Indanone derivatives, pharmaceutically acceptable salts or optical isomers thereof, preparation method for same, and pharmaceutical compositions containing same as active ingredient for preventing or treating viral diseases

ABSTRACT

Disclosed are novel indanone derivatives, pharmaceutically acceptable salts thereof or enantiomers, a preparation method thereof, and a pharmaceutical composition for the prevention or treatment of viral diseases, comprising the same as an active ingredient. The indanone derivatives have excellent inhibitory activity against picornaviruses including coxsackie-, entero-, echo-, Polio-, and rhinoviruses, as well as exhibiting low cytotoxicity, so that they can be useful as an active ingredient of a pharmaceutical composition for the prevention or treatment of viral diseases including poliomyelitis, paralysis, acute hemorrhagic conjunctivitis, viral meningitis, hand-foot-and-mouth disease, vesicular disease, hepatitis A, myositis, myocarditis, pancreatitis, diabetes, epidemic myalgia, encephalitis, cold, herpangina, foot-and-mouth disease, asthma, chronic obstructive pulmonary disease, pneumonia, sinusitis or otitis media.

CROSS REFERENCE TO RELATED APPLICATIONS

This patent application is a continuation application of non-provisionalapplication Ser. No. 14/126,485, filed Dec. 16, 2013, and titled“INDANONE DERIVATIVE, PHARMACEUTICALLY ACCEPTABLE SALT THEREOF ORENANTIOMER THEREOF, PREPARATION METHOD THEREOF, AND PHARMACEUTICALCOMPOSITION FOR PREVENTION OR TREATMENT OF VIRAL DISEASE COMPRISING THESAME”, the content of which is hereby incorporated by reference in itsentirety.

TECHNICAL FIELD

The present invention relates to indanone derivatives, pharmaceuticallyacceptable salts thereof or enantiomers thereof, preparation methodsthereof, and pharmaceutical compositions for the prevention andtreatment of viral diseases, comprising the same.

BACKGROUND ART

Picornaviruses are non-enveloped, positive single-stranded RNA viruseswith an RNA genome 7.2-8.5 Kb long. These viruses are very small andglobular in shape with a size of about 22˜30 nm, and were firstidentified a long time ago. Among the viruses belonging to the familyPicomaviridae are enteroviruses including rhinovirus, poliovirus,coxsackievirus A, coxsackievirus B, and echovirus, and hepatitis Avirus.

The diseases that picornaviruses cause are varied, ranging fromrespiratory diseases to digestive diseases, to circulatory diseases andto dermal diseases, examples of which include poliomyelitis, paralysis,acute hemorrhagic conjunctivitis, viral meningitis, hand-foot-and-mouthdisease, vesicular disease, hepatitis A, myositis, myocarditis,pancreatitis, diabetes, epidemic myalgia, encephalitis, cold,herpangina, and foot-and-mouth disease. However, there are notherapeutics for curing these diseases. Most of the drugs underdevelopment are uncoating inhibitors. Viruses belonging to the familyPicornaviridae cause various diseases including the aforementionedrespiratory diseases, which evoke hygienic, social and economic issues.Picornaviruses are the main causative agents of waterborne diseases.Being very stable and difficult to disinfect, the RNA virusesincessantly cause related diseases.

Human rhinoviruses (hRV) have been recently associated with the majorityof asthma exacerbations, and are known to exist even in bronchialtissues of many stable asthma patients. Comparison of respectivebronchial mucosa biopsy specimens taken from asthma and non-asthmapatients showed significantly higher frequencies of detection of humanrhinoviruses in the lower respiratory tract of asthma patients, comparedto non-asthma patients. It has also been reported that there iscorrelation between the presence of human rhinovirus and the clinicalseverity of asthma. In addition, rhinoviruses cause chronic obstructivepulmonary disease, pneumonia, sinusitis, and otitis media as well asasthma.

Rhinoviruses are the main causative of the common cold whileenterovirus-induced diseases include meningitis, respectory tractinfection, etc. Extensive effort to provide vaccination againstpoliovirus has significantly reduced the onset of poliomyelitisworldwide, but there are still reports of cases of the disease in Niger,Nigeria, Egypt, India, Pakistan, and Afghanistan. Hepatitis A is nowpossible to control to some degree thanks to vaccines for hepatitis Aviruses. However, no vaccines for coxsackieviruses, echoviruses, orrhinoviruses have been developed, thus far.

Particularly, coxsackievirus B is a main cause of myocarditis, which maydevelop, in serious cases, into idiopathic dilated cardiomyopathy, whichrequires heart transplantation

Enviroxime derivatives are considered the most promising candidate witha broad anti-enterovirus- and anti-rhinovirus activity. Enviroximeinterferes with the synthesis of plus-strand RNA by binding to the virusprotein 3A that is required for the formation of RNA intermediates inthe virus reproduction (Heinz B A and Vance L M: J Virol, 1995, 69(7),4189-97). In clinical studies, however, the compound was observed tohave insignificant or few therapeutic effects, with the concomitantdetection of bad pharmacokinetics and unwanted side effects (Miller F Det al.: Antimicrob Agents Chemother, 1985, 27(1), 102-6).

The protease inhibitor AG 7088 has been developed on the basis of theknowledge about the fine structure and function of the viral protease2C. In the cell culture in the nanomolar concentration range, AG 7088has an effect against 48 rhinovirus types and coxsackievirus A21, B3,enterovirus 70 and echovirus 11 (Pattick A K et al.: AntimicrobilaAgents Chemother, 1999, 43(10), 2444-50).

Thanks to the clarification of the molecular structure of the viralcapsids, the preconditions for a purposeful design of capsid blockers,the “WIN substances”, have been obtained (Diana G D: Curr Med Chem 2003,2, 1-12). They inhibit the adsorption and/or the uncoating ofrhinoviruses and enteroviruses. Some of the WIN substances have a highlyspecific effect only against individual genera or virus types of thepicornaviruses. Other derivatives inhibit the replication both ofrhinoviruses and enteroviruses. Arildone, disoxaril and pirodavirbelong, for example, to the WIN substances. These compounds showed verygood antiviral effects in the cell culture. However, a poor solubility(arildone), low bioavailability (arildone and disoxaril, a rapidmetabolization and excretion (disoxaril and WIN 54954) as well as sideeffects, such as skin rash (WIN 54954), made a clinical applicationimpossible.

Pleconaril, a kind of WIN substance, has a very good oralbioavailability and after its binding to the hydrophobe pocket in theviruscapsid, it inhibits the penetration of rhino-, echo- andcoxsackieviruses (Pevear D C et al.: Antimicrob Agents Chemother 1999,43(9), 2109-15; McKinlay M A et al.: Annu Rev Microbiol 1992, 46,635-54). Therefore, pleconaril is potentially effective against a broadspectrum of virus diseases, ranging from the common cold to the viralmeningitis or myocarditis. Resistances were observed for rhinoviruses,enterovirus 71 and coxsackievirus B3 (Ledford R M et al.: J Virol 2004,78(7), 3663-74; Groarke J M et al.: J Infect Dis 1999, 179(6), 1538-41).However, the proven therapeutic effect was not sufficient for theregistration of pleconaril (Picovir, Viropharma, USA) as an agent forthe treatment of rhinovirus infections in the USA. In March 2002, acorresponding application was refused by the Food and DrugAdministration (FDA) because therapy success was too low and sideeffects were observed.

BTA-798 was found to have higher antiviral activity than pleconaril, asevaluated in vitro and in vivo with rhinoviruses, and is now being undera clinical test (Ryan, J. et al. Antiviral Res [18th Intl Conf AntiviralRes (April 11-14, Barcelona) 2005]2005, 65(3): Abst LB-11).

However, no antiviral drugs that have gained approval for use in thetreatment of entero- or rhinoviruses have been developed, so far.

Leading to the present invention, intensive and thorough research intoeffective virustatics against picornaviruses including coxsackie-,entero-, echo-, polio-, and rhinoviruses, culminated in the finding thatnovel indanone derivatives exhibit highly inhibitory activity againstpicornaviruses including coxsackie-, entero-, echo-, polio-, andrhinoviruses.

DISCLOSURE Technical Problem

It is therefore an object of the present invention to provide a novelindanone derivative, a pharmaceutically acceptable salt thereof, or anenantiomer thereof.

It is another object of the present invention to provide a method forthe preparation of the indanone derivative, pharmaceutically acceptablesalt, or enantiomer.

It is a further object of the present invention to provide apharmaceutical composition for the prevention or treatment of a viraldisease, comprising the indanone derivative, pharmaceutically acceptablesalt, or enantiomer as an active ingredient.

Technical Solution

In accordance with an aspect thereof, the present invention provides anindanone derivative represented by the following Chemical Formula 1, apharmaceutically acceptable salt thereof, or an enantiomer thereof:

(wherein,

A¹, A², A³, A⁴, D, E, Z, G¹, G², G³, G⁴, X, and Y are respectively asdefined in the following description of the specification.)

In accordance with another aspect thereof, the present inventionprovides a method for the preparation of the indanone derivative,pharmaceutically acceptable salt or enantiomer.

In accordance with a further aspect thereof, the present inventionprovides a pharmaceutical composition for the prevention or treatment ofa viral disease, comprising the indanone derivative, pharmaceuticallyacceptable salt or enantiomer as an active ingredient.

Advantageous Effects

Having excellent inhibitory activity against picornaviruses includingcoxsackie-, entero-, echo-, Polio-, and rhinoviruses, as well asexhibiting low cytotoxicity, the indanone derivative of Chemical Formula1 can be useful as an active ingredient of a pharmaceutical compositionfor the prevention or treatment of viral diseases includingpoliomyelitis, paralysis, acute hemorrhagic conjunctivitis, viralmeningitis, hand-foot-and-mouth disease, vesicular disease, hepatitis A,myositis, myocarditis, pancreatitis, diabetes, epidemic myalgia,encephalitis, cold, herpangina, foot-and-mouth disease, asthma, chronicobstructive pulmonary disease, pneumonia, sinusitis or otitis media.

BEST MODE

Below, a detailed description will be given of the present invention.

According to one aspect thereof, the present invention addresses anindanone derivative represented by the following Chemical Formula 1, apharmaceutically acceptable salt thereof, or an enantiomer thereof:

wherein,

A¹, A², A³, and A⁴ are, independently or optionally, selected from thegroup consisting of —H, halogen, —OH, —CN, —N₃, alkoxy of C₁˜C₁₀, linearor branched alkyl of C₁˜C₁₀, 5-˜7-membered heterocycloalkylunsubstituted or substituted with —OH or methoxyphenylalkyl, aryl ofC₆˜C₁₂, —O(C═O)R¹, —(C═O)R¹, —(C═O)OR¹, —O(C═O)OR¹, —O(C═O)NR¹R², —NO₂,—NR¹R², —NR¹(C═O)R², —NR¹(C═S)R², —NR¹(C═O)OR², —NR¹(C═O)—NR²R³,—NR¹(SO₂)R², and —NR¹(C═S)—NR²R³, with a proviso that at least two ofA¹, A², A³ and A⁴ may form a ring together if they are adjacent to eachother;

D is —OH, halogen, linear or branched alkyl of C₁˜C₁₀, alkoxy of C₁˜C₁₀unsubstituted or substituted with phenyl, —O(CH₂)_(n)OH, —O(C═O)R¹,—(C═O)R¹, —(C═O)OR¹, —O(C═O)OR¹, —O(C═O)NR¹R², —NO₂, —NR¹R², —NR¹(O)R²,—NR¹(C═O)R², —NR¹(C═S)R², —NR¹(C═O)OR², —NR¹(C═O)—NR¹R², or—NR¹(C═S)—NR¹R²;

E is halogen, —OH, —CN, —N═C═O, —N₃, alkoxy of C₁˜C₁₀, —O(C═O)R¹,—(C═O)R¹, —(C═O)OR¹, —O(C═O)OR¹, —O(C═O)NR¹R², —NO₂, —NR¹R²,—NR¹(C═O)R², —NR¹(C═S)R², —NR¹(C═O)OR², —NR¹(C═O)—NR¹R²,—NR¹(C═O)NR²OR³, —NR¹(SO₂)R², —NR¹(C═S)—NR¹R², —NR¹(P═O)(OR²)₂, or

G¹, G², G³, and G⁴ are independently or optionally selected from thegroup consisting of —H, halogen, —OH, CN, alkoxy of C₁˜C₁₀, linear orbranched alkyl of C₁˜C₂₀, aryl of C₆˜C₁₂, —O(C═O)R¹, —(C═O)R¹,—(C═O)OR¹, —(CH₂)_(n)—(C═O)OR¹, —O(C═O)OR¹, —O(C═O)NR¹R², —NO₂, —NR¹R²,—NR¹(C═O)R², —NR¹(C═S)R², —NR¹(C═O)OR², —NR¹(C═O)—NR²R³, and—NR¹(C═S)—NR²R³, with a proviso that at least two of G¹, G², G³, and G⁴may form a ring together if they are adjacent to each other;

X is hydrogen, oxygen, sulfur, hydroxy, linear or branched alkyl ofC₁˜C₁₀, linear or branched alkylene of C₁˜C₁₀, ═N—NR¹R², —NR¹—OR², or═N—OR¹;

Y is —O—, —CH₂—, —NH—, or —(NR⁵)—;

R⁵ is —(C═O)H, —(C═O)OH, —(C═O)R¹, —(C═S)R¹, or —(C═O)OR¹;

Z is C or N;

R¹, R², R³, and R⁴ are independently hydrogen, linear or branched alkylof C₁˜C₁₀, linear or branched alkylene of C₁˜C₁₀ unsubstituted orsubstituted with phenyl, cycloalkyl of C₃˜C₇, heterocycloalkyl of C₃˜C₇,aryl of C₆˜C₁₂, or 5-˜14-membered heteroaryl;

wherein the heterocycloalkyl may be substituted with at least one oxygenatom via a double bond,

the aryl is mono- or bicyclic and may have at least one substituentselected from the group consisting of halogen, —CN, phenyl, linear orbranched alkyl of C₁˜C₆, R⁵, and alkoxy of C₁˜C₆,

the heteroaryl is mono-, bi- or tricyclic, and may have at least onesubstituent selected from the group consisting of halogen, —OH, —NO₂,—NH₂, —CN, ═O or —O⁻, linear or branched alkyl of C₁˜C₁, linear orbranched alkoxy of C₁˜C₁₀, and phenyl,

the linear or branched alkyl may be unsubstituted or substituted with atleast one substituent selected from the group consisting of phenyl,halogen, 5-˜7-membered heteroaryl, and —NHBoc,

the phenyl may be substituted with at least one selected from the groupconsisting of halogen, phenyl, or phenyl-substituted alkoxy of C₁˜C₆,

the heterocycloalkyl or heteroaryl contains at least one heteroatomselected from the group consisting of N, O, and S,

the halogen is F, Cl, Br, or I,

n is an integer of 1˜10, and

‘

’ represents a single or double bond.

In a preferred embodiment,

A¹, A², A³, and A⁴ are, independently or optionally, selected from thegroup consisting of —H, alkoxy of C₁˜C₅, linear or branched alkyl ofC₁˜C₅, 5-˜7-membered heterocycloalkyl unsubstituted or substituted with—OH or methoxyphenylalkyl, aryl of C₆˜C₁₂, —NO₂, and —NR¹R²;

D is —OH, halogen, linear or branched alkyl of C₁˜C₅, or alkoxy of C₁˜C₅unsubstituted or substituted with phenyl;

E is halogen, —OH, or alkoxy of C₁˜C₅;

E is halogen, —OH, alkoxy of C₁˜C₅, —NR¹(C═O)R², —NR¹(C═O)OR², or—NR¹(C═O)—NR¹R²;

G¹, G², G³, and G⁴ are, independently or optionally, selected from thegroup consisting of —H, alkoxy of C₁˜C₅, and linear or branched alkyl ofC₁˜C₁₆;

X is oxygen, hydroxyl, or linear or branched alkyl of C₁˜C₅;

Y is —O— or —CH₂—;

Z is C or N;

R¹, R², R³, and R⁴ are independently hydrogen, linear or branched alkylof C₁˜C₇, heterocycloalkyl of C₃˜C₇, aryl of C₆˜C₁₂, or 5-˜14-memberedheteroaryl;

wherein the heterocycloalkyl may be substituted with at least one oxygenatom via a double bond,

the aryl is mono- or bicyclic and may have at least one substituentselected from the group consisting of halogen, phenyl, linear orbranched alkyl of C₁˜C₃, and alkoxy of C₁˜C₃,

the heteroaryl is mono-, bi- or tricyclic, and may have at least onesubstituent selected from the group consisting of halogen, —OH, —NO₂,—NH₂, —CN, ═O or —O⁻, linear or branched alkyl of C₁˜C₁₀, linear orbranched alkoxy of C₁˜C₁₀, and phenyl,

the linear or branched alkyl may be unsubstituted or substituted with atleast one substituent selected from the group consisting of phenyl,halogen, and 5-˜7-membered heteroaryl,

the phenyl may be substituted with at least one selected from the groupconsisting of halogen, and phenyl,

the hetetrocycloalkyl or heteroaryl contains at least one heteroatomselected from the group consisting of N, O, and S,

the halogen is F, or Cl, and

‘

’ represents a single or double bond.

In a more preferred embodiment,

A¹, A², A³, and A⁴ are, independently or optionally, selected from thegroup consisting of —H and —NR¹R²;

D is —OH;

E is —OH or —NR¹(C═O)R²;

G¹, G², G³, and G⁴ are, independently or optionally, linear or branchedalkyl of C₁˜C₁₅;

X is oxygen;

Y is —O—;

Z is C;

R¹, R², R³, and R⁴ are, independently, hydrogen or 5-˜14-memberedheteroaryl;

wherein, the 5-˜14-membered heteroaryl is monocyclic, bicyclic, ortricyclic, and may be substituted with a substituent selected from thegroup consisting of halogen, —OH, —NO₂, —NH₂, —CN, ═O or —O⁻, linear orbranched alkyl of C₁˜C₁₀, linear or branched alkoxy of C₁˜C₁₀, andphenyl,

the phenyl may be substituted with at least one selected form the groupconsisting of halogen and phenyl,

the heteroaryl contains a heteroatom selected from the group consistingof N, O, and S, and

the halogen is F or Cl, and

‘

’ represents a single or double bond.

In a further more preferred embodiment,

A¹, A², and A³ are —H, and A⁴ is —NH₂;

D is —OH;

E is —NR¹(C═O)R²;

G¹, G³ and G⁴ are —H, and G² is isopropyl;

X is oxygen;

Y is —O—;

Z is C;

R¹ is hydrogen and R² is 5-˜14-membered heteroaryl;

wherein the heteroaryl is furane, benzofurane, pyridine,pyrazolopyridine, pyrimidine, pyrazolopyrimidine, pyrazine, thiopene,quinoline, isoquinoline, triazole, thiazole, indole, pyrazole, indazole,tetrazole, benzotriazole, chromene, pyrane, pyrrole, benzopyrazole,isoxazole, xanthene, cinnoline, imidazole, benzoimidazole, acridine,imidazopyridine, imidazopyrimidine, quinoxaline, pyridazine,tetrazolopyridine, triazolopyridine, triazolopyrimidine or indolizine,and may be substituted with at least one substituent selected from thegroup consisting of halogen, —OH, —NO₂, —NH₂, —CN, ═O or —O⁻, linear orbranched alkyl of C₁˜C₁₀, linear or branched alkoxy of C₁˜C₁₀, andphenyl, and

the halogen is F or Cl, and

‘

’ represents a double bond.

Concrete examples of the compound represented by Chemical Formula 1include:

-   1)    4b,9b-dihydroxy-7-methyl-4bH-benzo[d]indeno[1,2-b]furan-10(9bH)-one;-   2)    7-methyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furane-4b,9b-diyl    diacetate;-   3) ethyl    2-(4b,9b-dihydroxy-6-methoxy-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furane-8-yl)acetate;-   4)    4b,9b-dihydroxy-7,8-dimethyl-4bH-benzo[d]indeno[1,2-b]furan-10(9bH)-one;-   5) 2-hydroxy-2-(2-hydroxyphenyl)-1H-indene-1,3(2H)-dione;-   6) 2-(5-fluoro-2-hydroxyphenyl)-2-hydroxy-1H-indene-1,3(2H)-dione;-   7)    4b,9b-dihydroxy-7-methoxy-4bH-benzo[d]indeno[1,2-b]furan-10(9bH)-one;-   8)    6,7-dichloro-4b,9b-dihydroxy-4bH-benzo[d]indeno[1,2-b]furan-10(9bH)-one;-   9)    7-ethyl-4b,9b-dihydroxy-4bH-benzo[d]indeno[1,2-b]furan-10(9bH)-one;-   10)    4b,9b-dihydroxy-7-isopropyl-4bH-benzo[d]indeno[1,2-b]furan-10(9bH)-one;-   11)    7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furane-4b,9b-diyl    diacetate;-   12)    4b,9b-dihydroxy-8-methoxy-4bH-benzo[d]indeno[1,2-b]furan-10(9bH)-one;-   13)    4b,9b-dihydroxy-6-phenyl-4bH-benzo[d]indeno[1,2-b]furan-10(9bH)-one;-   14)    4b,9b-dihydroxy-8-nitro-4bH-benzo[d]indeno[1,2-b]furan-10(9bH)-one;-   15) 4b,11b-dihydroxy-4bH-indeno[1,2-b]naphtho[2,3-d]furan-12(11    bH)-one;-   16) 6b,11b-dihydroxy-6bH-indeno[1,2-b]naphtho[2,1-d]furan-7(11    bH)-one;-   17)    4b,9b-dihydroxy-8-propyl-4bH-benzo[d]indeno[1,2-b]furan-10(9bH)-one;-   18)    8-ethyl-4b,9b-dihydroxy-4bH-benzo[d]indeno[1,2-b]furan-10(9bH)-one;-   19)    8-sec-butyl-4b,9b-dihydroxy-4bH-benzo[d]indeno[1,2-b]furan-10(9bH)-one;-   20)    8-tert-butyl-4b,9b-dihydroxy-4bH-benzo[d]indeno[1,2-b]furan-10(9bH)-one;-   21)    6-tert-butyl-4b,9b-dihydroxy-4bH-benzo[d]indeno[1,2-b]furan-10(9bH)-one;-   22)    4b,9b-dihydroxy-7,8,9-trimethyl-4bH-benzo[d]indeno[1,2-b]furan-10(9bH)-one;-   23)    4b,9b-dihydroxy-8-tert-pentyl-4bH-benzo[d]indeno[1,2-b]furan-10(9bH)-one;-   24)    6,8-di-tert-butyl-4b,9b-dihydroxy-4bH-benzo[d]indeno[1,2-b]furan-10(9bH)-one;-   25)    6,8-di-tert-butyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furane-4b,9b-diyl    diacetate;-   26)    4b,9b-dihydroxy-8-nonyl-4bH-benzo[d]indeno[1,2-b]furan-10(9bH)-one;-   27)    4b,9b-dihydroxy-8-pentadecyl-4bH-benzo[d]indeno[1,2-b]furan-10(9bH)-one;-   28)    6,8-bis-(1,1-dimethyl-propyl)-4b,9b-dihydroxy-4b,9b-dihydro-5-oxa-indeno[2,1-a]inden-10-one;-   29) isopropyl    4b,9b-dihydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-1-ylcarbamate;-   30) 2,6′-dihydroxy-2′,3′-dihydro-1′H-[2,5′]biindenyl-1,3-dione;-   31)    6b,11b-dihydroxy-1,2,3,4,6b,11b-hexahydro-12-oxa-benzo[4,5]pentaleno[2,1-a]naphthalen-7-one;-   32)    4b,9b-dihydroxy-7-isopropyl-2-methoxy-4b,9b-dihydro-5-oxa-indeno[2,1-a]inden-10-one;-   33)    7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-4b,9b-diyl    bis(2,2-dimethylpropanoate);-   34)    (2E,2′E)-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-4b,9b-diyl    bis(3-phenylacrylate);-   35)    9b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-4b-yl    acrylate;-   36)    9b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno-b]furan-4b-yl    furane-2-carboxylatefurane-2-carboxylic acid;-   37) diethyl    7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furane-4b,9b-diyl    dicarbonate;-   38) ethyl    9b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-4b-yl    carbonate;-   39) methyl    4b,9b-dihydroxy-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-8-carboxylate;-   40)    9b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-4b-yl    diethylcarbamate;-   41)    4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl    diethylcarbamate;-   42)    2,3-difluoro-4b,9b-dihydroxy-7-isopropyl-4bH-benzo[d]indeno[1,2-b]furan-10(9bH)-one;-   43)    1,4b,9b-trihydroxy-7-isopropyl-4bH-benzo[d]indeno[1,2-b]furan-10(9bH)-one;-   44)    4b,9b-dihydroxy-7-isopropyl-1H-cyclopenta[b]naphthaleno[1,2-b]furan-10(9bH)-one;-   45)    9b-hydroxy-7-isopropyl-4b-methoxy-1-nitro-4bH-benzo[d]indeno[1,2-b]furan-10(9bH)-one;-   46)    1-amino-4b,9b-dihydroxy-7-isopropyl-4bH-benzo[d]indeno[1,2-b]furan-10(9bH)-one;-   47)    1-amino-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furane-4b,9b-diyl    diacetate;-   48)    N-(4b,9b-dihydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-1-yl)acetamide;-   49) methyl    4b,9b-dihydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-1-ylcarbamate;-   50)    1-amino-7-ethyl-4b,9b-dihydroxy-4b,9b-dihydro-5-oxa-indeno[2,1-a]inden-10-one;-   51)    7-ethyl-4b,9b-dihydroxy-1-nitro-4b,9b-dihydro-5-oxa-indeno[2,1-a]inden-10-one;-   52)    7-ethyl-2,4b,9b-trihydroxy-4b,9b-dihydro-5-oxa-indeno[2,1-a]inden-10-one;-   53) acetic acid    4b-acetoxy-1-amino-7-isopropyl-10-oxo-4b,10-dihydro-5-oxa-indeno[2,1-a]inden-9b-yl    ester;-   54) acetic acid    4b-acetoxy-7-isopropyl-1-methanesulfonylamino-10-oxo-4b,10-dihydro-5-oxa-indeno[2,1-a]inden-9b-yl    ester;-   55)    1-(4b,9b-dihydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-1-yl)-3-isopropylurea;-   56)    N-(9b-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-1-yl)acetamide;-   57)    N,N′-(4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furane-1,9b-diyldiacetamide;-   58)    N-(7-amino-2-hydroxy-2-(4-isopropyl-2-hydroxyphenyl)-1,3-dioxo-2,3-dihydro-1H-inden-4-yl)acetamide;-   59)    N-(2-amino-4b,9b-dihydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-1-yl)acetamide;-   60)    1-amino-4b,9b-dihydroxy-7-isopropyl-2-nitro-4bH-indeno[1,2-b]benzofuran-10(9bH)-one;-   61)    1,4-diamino-4b,9b-dihydroxy-7-isopropyl-4bH-benzo[d]indeno[1,2-b]furan-10(9bH)-one;-   62)    1,2-diamino-4b,9b-dihydroxy-7-isopropyl-4bH-indeno[1,2-b]benzofuran-10(9bH)-one;-   63)    2-(2-hydroxy-4-isopropylphenyl)-1,3-dioxo-2,3-dihydro-1H-inden-2-yl    dimethylcarbamate;-   64)    4b,9b-dihydroxy-6,8-diisopropyl-4b,9b-dihydro-5-oxa-indeno[2,1-a]inden-10-one;-   65)    9b-amino-4b-hydroxy-7-isopropyl-4b,9b-dihydro-5-oxa-indeno[2,1-a]inden-10-one;-   66)    N-(4b-hydroxy-7-isopropyl-10-oxo-4b,10-dihydro-5-oxa-indeno[2,1-a]inden-9b-yl)-acetamide;-   67)    9b-hexylamino-4b-hydroxy-7-isopropyl-4b,9b-dihydro-5-oxa-indeno[2,1-a]inden-10-one;-   68)    9b-amino-4b-hydroxy-6,8-diisopropyl-4b,9b-dihydro-5-oxa-indeno[2,1-a]inden-10-one;-   69)    4b-hydroxy-9b-isocyanato-7-isopropyl-4b,9b-dihydro-5-oxa-indeno[2,1-a]-inden-10-one;-   70)    (9b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-5-oxa-indeno[2,1-a]inden-4b-yl)-carbamic    acid methyl ester;-   71) pentanoic acid    (9b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-5-oxa-indeno[2,1-a]inden-4b-yl-amide;-   72)    N-(9b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-5-oxa-indeno[2,1-a]inden-4b-yl)-isobutylamide;-   73)    N-(1-amino-9b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-5-oxa-indeno[2,1-a]inden-4b-yl)-acetamide;-   74)    N-(9b-hydroxy-6,8-diisopropyl-10-oxo-9b,10-dihydro-5-oxa-indeno[2,1-a]inden-4b-yl)-acetamide;-   75)    N-(9b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-5-oxa-indeno[2,1-a]inden-4b-yl)-N-methyl-acetamide;-   76)    1-(4b-hydroxy-7-isopropyl-1-nitro-10-oxo-4b,10-dihydro-5-oxa-indeno[2,1-a]inden-9b-yl-3-isopropyl-urea;-   77)    N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-4b,10-dihydro-5-oxa-indeno[2,1-a]inden-9b-yl-isobutylamide;-   78) pentanoic acid    (1-amino-4b-hydroxy-7-isopropyl-10-oxo-4b,10-dihydro-5-oxa-indeno[2,1-a]inden-9b-yl-amide;-   79)    9b-hydroxy-4b-(2-hydroxyethoxy)-7-isopropyl-4bH-benzo[d]indeno[1,2-b]furan-10(9bH)-one;-   80)    4b,9b-dihydroxy-7-isopropyl-1-nitro-4bH-benzo[d]indeno[1,2-b]furan-10(9bH)-one;-   81)    4b,9b-dihydroxy-7-isopropyl-2,3-dimethoxy-4bH-benzo[d]indeno[1,2-b]furan-10(9bH)-one;-   82)    4b,9b-dihydroxy-7-isopropyl-2,3-dimethyl-4bH-benzo[d]indeno[1,2-b]furan-10(9bH)-one;-   83) a mixture of 6:4    (4bS,9bS)-2-bromo-4b,9b-dihydroxy-7-isopropyl-4bH-benzo[d]indeno[1,2-b]furan-10(9bH)-one    and    (4bS,9bS)-3-bromo-4b,9b-dihydroxy-7-isopropyl-4bH-benzo[d]indeno[1,2-b]furan-10(9bH)-one;-   84) methyl    (4bS,9bS)-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-ylcarbamate;-   85) isopropyl    (4bS,9bS)-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-ylcarbamate;-   86)    ethyl(4bS,9bS)-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-ylcarbamate;-   87)    N,N′-((4bS,9bS)-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furane-1,9b-diyl)diacetamide;-   88)    4b,9b-dihydroxy-7-isopropyl-4bH-indeno[1,2-b]benzofuran-10(9bH)-one    O-methyl oxime;-   89) butyric acid    9b-butyrylamino-7-isopropyl-10-oxo-9b,10-dihydro-5-oxa-indeno[2,1-a]inden-4b-yl    ester;-   90) octanoic acid    [2-(2-hydroxy-4-isopropyl-phenyl)-1,3-dioxo-indan-2-yl]-amide;-   91) hexanoic acid    9b-hexanoylamino-7-isopropyl-10-oxo-9b,10-dihydro-5-oxa-indeno[2,1-a]inden-4b-yl    ester;-   92) heptanoic acid    9b-heptanoylamino-7-isopropyl-10-oxo-9b,10-dihydro-5-oxa-indeno[2,1-a]inden-4b-yl    ester;-   93)    N-((4bS,9bS)-1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)octanamide;-   94)    (4bR,9bS)-1-amino-7-isopropyl-10-oxo-9b-propionamido-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-4b-yl    propionate;-   95)    (4bR,9bS)-1-amino-9b-butyramido-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-4b-yl    butyrate;-   96)    1-amino-7-isopropyl-10-oxo-9b-pentanamido-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-4b-yl    pentanoate;-   97)    1-amino-9b-hexanamido-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-4b-yl    hexanoate;-   98)    (4bS,9bS)-4b-hydroxy-7-isopropyl-9b-methoxy-4bH-indeno[1,2-b]benzofuran-10(9bH)-one;-   99)    1-amino-9b-heptanamido-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-4b-yl    heptanoate;-   100)    1-((4bS,9bS)-7-isopropyl-4b-methoxy-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)urea;-   101)    1-((4bS,9bS)-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl-3-methylurea;-   102)    1-ethyl-3-((4bS,9bS)-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)urea;-   103)    1-((4bS,9bS)-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl-3-methoxyurea;-   104)    5-acetyl-4b,9b-dihydroxy-7,8-dimethyl-4b,5-dihydroindeno[1,2-b]indol-10(9bH)-one;-   105)    4b,9b-dihydroxy-7,8-dimethyl-5-propionyl-4b,5-dihydroindeno[1,2-b]indol-10(9bH)-one;-   106)    4b,9b-dihydroxy-7,8-dimethyl-4b,5-dihydroindeno[1,2-b]indol-10(9bH)-one;-   107)    5-acetyl-7,8-dimethyl-10-oxo-4b,5,9b,10-tetrahydroindeno[1,2-b]indole-4b,9b-diyl    diacetate;-   108)    5-acetyl-9b-amino-4b-hydroxy-5,9b-dihydro-4bH-indeno[1,2-b]indol-10-one;-   109)    N-(9b-amino-4b-hydroxy-7-isopropyl-4-nitro-10-oxo-9b,10-dihydro-4bH-5-oxa-indeno[2,1-a]inden-1-yl)-acetamide;-   110) acetic acid    1,9b-bis-acetylamino-7-isopropyl-4-nitro-10-oxo-9b,10-dihydro-5-oxa-indeno[2,1-a]inden-4b-yl    ester;-   111)    9b-acetamido-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-4b-yl    methyl carbonate;-   112)    9b-acetamido-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-4b-yl    pentanoate;-   113)    9b-acetamido-1-amino-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-4b-yl    methyl carbonate;-   114)    N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)pivalamide;-   115)    9b-acetamido-1-amino-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-4b-yl    butyl carbonate;-   116)    9b-acetamido-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-4b-yl    ethyl carbonate;-   117)    9b-acetamido-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-4b-yl    pivalate;-   118)    9b-acetamido-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-4b-yl    methylcarbamate;-   119)    N,N′-(7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofurane-4b,9b-diyl)diacetamide;-   120)    4b-(benzyloxy)-9b-hydroxy-7-isopropyl-4bH-indeno[1,2-b]benzofuran-10(9bH)-one;-   121) carbonic acid    9b-acetylamino-7-isopropyl-10-oxo-9b,10-dihydro-5-oxa-indeno[2,1-a]inden-4b-yl    ester phenyl ester;-   122) phenyl-thiocarbamic acid    O-(9b-azido-7-isopropyl-10-oxo-9b,10-dihydro-5-oxa-indeno[2,1-a]inden-4b-yl    ester;-   123)    9b-acetamido-1-amino-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-4b-yl    ethyl carbonate;-   124)    N,N′-(7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofurane-4b,9b-diyldipropionamide;-   125)    N,N′-(7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofurane-4b,9b-diylbis(2-methylpropanamide);-   126)    4b,9b-dihydroxy-7-isopropyl-4bH-benzofuro[2′,3′:3,4]cyclopenta[1,2-b]pyridin-10(9bH)-one;-   127)    10-hydroxy-7-isopropyl-9b,10-dihydro-4bH-indeno[1,2-b]benzofurane-4b,9b-diyl    diacetate;-   128)    9b-hydroxy-7-isopropyl-4b-(methoxyamino)-4bH-indeno[1,2-b]benzofuran-10(9bH)-one    O-methyl oxime;-   129)    7-isopropyl-4b-methoxy-10-methylene-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-ol;-   130)    9b-hydroxy-7-isopropyl-4b-methoxy-4bH-indeno[1,2-b]benzofuran-10(9bH)-one    O-methyl oxime;-   131) a mixture of 1-bromo and    4-bromo-4b,9b-dihydroxy-7-isopropyl-4bH-indeno[1,2-b]benzofuran-10(9bH)-one;-   132)    1-(benzylamino)-4b,9b-dihydroxy-7-isopropyl-4bH-indeno[1,2-b]benzofuran-10(9bH)-one;-   133)    1-(ethylamino)-4b,9b-dihydroxy-7-isopropyl-4bH-indeno[1,2-b]benzofuran-10(9bH)-one;-   134)    9b-hydroxy-7-isopropyl-4b-methyl-4bH-indeno[1,2-b]benzofuran-10(9bH)-one;-   135)    4b,9b-dihydroxy-5-isobutyryl-7,8-dimethyl-4b,5-dihydroindeno[1,2-b]indol-10(9bH)-one;-   136)    7-isopropyl-10-methyl-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-4b,9b-diol;-   137)    N-(1-bromo-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)acetamide;-   138)    4b,9b-dihydroxy-5-isobutyryl-7,8-dimethoxy-5,9b-dihydro-4bH-indeno[1,2-b]indol-10-one;-   139)    4b,9b-dihydroxy-7-isopropyl-2-piperidinyl-4bH-benzo[d]indeno[1,2-b]furan-10(9bH)-one;-   140)    4b,9b-dihydroxy-7-isopropyl-2-morpholinyl-4bH-benzo[d]indeno[1,2-b]furan-10(9bH)-one;-   141)    4b,9b-dihydroxy-7-isopropyl-1-piperidinyl-4bH-benzo[d]indeno-[1,2-b]furan-10(9bH)-one;-   142)    4b,9b-dihydroxy-7-isopropyl-1-morpholinyl-4bH-benzo[d]indeno[1,2-b]furan-10(9bH)-one;-   143)    N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)propionamide;-   144)    N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)butyramide;-   145)    4b,9b-dihydroxy-5-isobutyryl-7-isopropyl-5,9b-dihydro-4bH-indeno[1,2-b]indol-10-one;-   146)    4b,9b-dihydroxy-7-isopropyl-2-(hydroxypiperidinyl)-4bH-benzo[d]indeno[1,2-b]furan-10(9bH)-one;-   147)    4b,9b-dihydroxy-1-(4-hydroxypiperidin-1-yl)-7-isopropyl-4bH-benzo[d]indeno[1,2-b]furan-10(9bH)-one;-   148)    4b,9b-dihydroxy-7-isopropyl-2-(4-(4-methoxybenzyl)piperazin-1-yl)-4bH-benzo[d]indeno[1,2-b]furan-10    (9 bH)-one;-   149)    4b,9b-dihydroxy-7-isopropyl-1-(4-(4-methoxybenzyl)piperazin-1-yl)-4bH-benzo[d]indeno[1,2-b]furan-10    (9 bH)-one;-   150)    2-(dimethylamino)-4b,9b-dihydroxy-7-isopropyl-4bH-benzo[d]indeno[1,2-b]-furan-10(9bH)-one;-   151)    1-(dimethylamino)-4b,9b-dihydroxy-7-isopropyl-4bH-benzo[d]indeno[1,2-b]-furan-10(9bH)-one;-   152)    10-hydrazono-7-isopropyl-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-4b,9b-diol;-   153)    N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)benzamide;-   154)    N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-3-methoxybenzamide;-   155)    N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-4-chlorobenzamide;-   156)    N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-4-nitrobenzamide;-   157) 1-amino-4b,9b-dihydroxy-6,8-diisopropyl-4    bH-benzo[d]indeno[1,2-b]furan-10(9bH)-one;-   158)    N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)cyclopropanecarboxamide;-   159)    1-(4b-hydroxy-6,8-diisopropyl-1-amino-10-oxo-9b,10-dihydro-4bH-benzo[d]-indeno[1,2-b]furan-9b-yl)-3-(4-methoxyphenyl)thiourea;-   160)    1-(4b-hydroxy-6,8-diisopropyl-1-amino-10-oxo-9b,10-dihydro-4bH-benzo[d]-indeno[1,2-b]furan-9b-yl)-3-(phenyl)thiourea;-   161)    N-(4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)thiophene-2-carboxamide;-   162)    1-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-3-(4-methoxyphenyl)urea;-   163)    1-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-3-butylurea;-   164)    1-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-3-(4-fluorophenyl)urea;-   165)    1-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-3-(tert-butyl)urea;-   166)    N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)formamide;-   167)    N-(1-formamido-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]-indeno[1,2-b]furan-9b-yl)acetamide;-   168)    N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)methanesulfonamide;-   169) diethyl    (1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)phosphoamidate;-   170)    N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-4-cyanobenzamide;-   171)    N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-2-naphthamide;-   172)    N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-[1,1′-biphenyl]-4-carboxamide;-   173)    1-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)-3-ethylurea;-   174)    N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)tetrahydrofurane-2-carboxamide;-   175)    N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-2,2,2-trifluoroacetamide;-   176)    N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)-1,1,1-trifluoromethanesulfonamide;-   177)    N-(4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)formamide;-   178)    1,1,1-trifluoro-N-(4b-hydroxy-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)methanesulfonamide;-   179)    N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-2-phenylacetamide;-   180)    (E)-N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-3-(3,4-dichlorophenyl)acrylamide;-   181)    N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-4-(benzyloxy)benzamide;-   182)    2-([1,1-biphenyl]-4-yl)-N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)acetamide;-   183)    N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-2-methoxybenzamide;-   184)    tert-butyl(2R)-1-(4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-ylamino)-1-oxopropan-2-ylcarbamate;-   185)    tert-butyl(2R)-1-(4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-ylamino)-1-oxo-3-phenylpropan-2-ylcarbamate;-   186)    N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)-2-methylbenzamide;-   187)    N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)-3-methylbenzamide;-   188)    N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)-4-methylbenzamide;-   189)    methyl-4-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-ylcarbamoyl)benzoate;-   190)    N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-3-chlorobenzamide;-   191)    N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-3,5-dimethylbenzamide;-   192)    N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-2,4,6-trichlorobenzamide;-   193)    N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)-2-fluoroacetamide;-   194)    N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)-2-chloroacetamide;-   195)    N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)-2,2-dichloroacetamide;-   196) 1-amino-9b-(4-butyl-1H-1,2,3-triazol-1-yl)-4b-hydroxy-7-iso    propy-4bH-indeno[1,2-b]benzofuran-10(9bH)-one;-   197)    N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)picolinamide;-   198)    N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)nicotinamide;-   199)    N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)isonicotinamide;-   200)    N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)pirazine-2-carboxamide;-   201)    N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)furane-2-carboxamide;-   202)    N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)quinoline-8-carboxamide;-   203)    N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)quinoline-6-carboxamide;-   204)    N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)    benzofurane-2-carboxamide;-   205)    N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)-3-methylbenzofurane-2-carboxamide;-   206)    N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-4-methylthiazole-5-carboxamide;-   207)    (4R)—N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-2-oxothiazolidine-4-carboxamide;-   208)    N-(4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-1H-indole-2-carboxamide;-   209)    N-(4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-1H-indole-3-carboxamide;-   210)    N-(4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)formamide;-   211)    N-(4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-1-phenyl-5-(trifluoromethyl)-1H-pyrazole-4-carboxamide;-   212)    N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)-1H-indazole-3-carboxamide;-   213)    N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)-2-(1H-tetrazol-1-yl)acetamide;-   214)    N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)quinoline-3-carboxamide;-   215)    N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)quinoline-4-carboxamide;-   216)    N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-5-methylthiophene-2-carboxamide;-   217)    N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-2-methoxythiophene-3-carboxamide;-   218)    N-(4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)picolinamide;-   219)    N-(4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)pyrimidine-4-carboxamide;-   220)    N-(4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)-2-(1H-tetrazol-5-yl)acetamide;-   221)    N-(4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)-1H-benzo[d][1,2,3]triazole-5-carboxamide;-   222)    N-(4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)-1H-1,2,4-triazole-3-carboxamide;-   223)    N-(4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)-5-nitrothiophene-2-carboxamide;-   224)    N-(4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)-2,6-dioxo-1,2,3,6-tetrahydropyrimidine-4-carboxamide;-   225)    N-(4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)-2-oxo-2H-chromene-3-carboxamide;-   226)    N-(4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)-2-oxo-2H-pyrane-5-carboxamide;-   227)    N-(4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)-1H-benzo[d]imidazole-2-carboxamide;-   228)    N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-3-(2-chloro-6-fluorophenyl)-5-methylisooxazole-4-carboxamide;-   229)    N-(4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-3-phenyl-1H-pyrazole-5-carboxamide;-   230)    N-(4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)nicotinamide;-   231)    N-(1-amino4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-2-oxo-2-(thiophen-2-yl)acetamide;-   232)    5-amino-N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)furane-2-carboxamide;-   233)    N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-1H-pyrrole-2-carboxamide;-   234)    N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-2-methoxyisonicotinamide;-   235)    N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)benzo[b]thiophene-2-carboxamide;-   236)    3-(2,6-dichlorophenyl)-N-(4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)-5-methylisooxazole-4-carboxamide;-   237)    N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)-9H-xanthene-9-carboxamide;-   238)    N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)cinnoline-4-carboxamide;-   239)    N-(4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)cinnoline-4-carboxamide;-   240)    N-(4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)-1H-benzo[d]imidazole-5-carboxamide;-   241)    N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)acridine-9-carboxamide;-   242)    N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)-4-nitro-1H-pyrazole-3-carboxamide;-   243)    N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)-4-methylpicolinamide;-   244)    N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)-4-(trifluoromethyl)picolinamide;-   245)    N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)-5-cyanopicolinamide;-   246)    N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)-3-chloropicolinamide;-   247)    N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)-4-methoxyquinoline-2-carboxamide;-   248)    N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)isoquinoline-3-carboxamide;-   249)    N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-2-methylisonicotinamide;-   250)    N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-3-fluoroisonicotinamide;-   251)    N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-3-chloroisonicotinamide;-   252)    N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-1-methyl-1H-imidazole-2-carboxamide;-   253)    2-((1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)carbamoyl)pyridine    1-oxide;-   254)    N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-4-chloronicotinamide;-   255)    N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-5-fluoronicotinamide;-   256)    N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-5-hydroxynicotinamide;-   257)    N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-3-hydroxypicolinamide;-   258)    N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-4-methylnicotinamide;-   259)    N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-5-methylnicotinamide;-   260)    N-(1-amino-4b-hydroxy-7,8-dimethyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)nicotinamide;-   261)    N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-5-methoxynicotinamide;-   262)    N-(1-amino-4b-hydroxy-7,8-dimethyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)quinoline-6-carboxamide;-   263)    N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)quinoline-2-carboxamide;-   264)    N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)-3-bromobenzo[b]thiophene-2-carboxamide;-   265)    N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)-1H-indole-2-carboxamide;-   266)    N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)isoquinoline-1-carboxamide;-   267)    N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-6-fluoro-4-methoxyquinoline-3-carboxamide;-   268)    N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-1-methyl-1H-indole-2-carboxamide;-   269)    N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-3-chloro-6-fluorobenzo[b]thiophene-2-carboxamide;-   270)    N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-3-chloro-6-methylbenzo[b]thiophene-2-carboxamide;-   271)    N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-1,3-dimethyl-1H-pyrazolo[3,4-b]pyridine-5-carboxamide;-   272)    N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)imidazo[1,2-a]pyridine-6-carboxamide;-   273)    N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)pyrazolo[1,5-a]pyrimidine-2-carboxamide;-   274)    N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-3-methyl    benzo[b]thiophene-2-carboxamide;-   275)    N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)quinoxaline-2-carboxamide;-   276)    N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)pyridazine-4-carboxamide;-   277)    N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)quinoxaline-6-carboxamide;-   278)    N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)tetrazolo[1,5-a]pyridine-6-carboxamide;-   279)    N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)tetrazolo[1,5-a]pyridine-8-carboxamide;-   280)    N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-7-methylimidazo[1,2-a]pyridine-2-carboxamide;-   281)    N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-7-methyl-[1,2,4]triazolo[1,5-a]pyrimidine-2-carboxamide;-   282)    N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-5,7-dimethylpyrazolo[1,5-a]pyrimidine-3-carboxamide;-   283)    N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)indolizine-2-carboxamide;-   284)    N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-1,6-diisopropyl-1H-pyrazolo[3,4-b]pyridine-4-carboxamide;-   285)    N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)imidazo[1,2-a]pyrimidine-2-carboxamide;-   286)    N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-1-oxo-1,2-dihydroisoquinoline-3-carboxamide;-   287)    N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)-3-methylimidazo[1,5-a]pyridine-1-carboxamide;-   288)    N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)-2H-indazole-3-carboxamide;-   289)    N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-7-methylpyrazolo[1,5-a]pyrimidine-6-carboxamide;-   290)    N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-1H-benzo[d]imidazole-2-carboxamide;-   291)    N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-5-fluoro-1H-benzo[d]imidazole-2-carboxamide;-   292)    N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)tetrazolo[1,5-a]pyridine-5-carboxamide;-   293)    N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-1-methyl-1H-indazole-3-carboxamide;-   294)    N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-1H-indole-5-carboxamide;-   295) N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-b,    O-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-1-methyl-3a,7a-dihydro-1H-indazole-3-carboxamide;-   296)    N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-1-methyl-1H-imidazole-4-carboxamide;-   297)    N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-1H-pyrrole-3-carboxamide;-   298)    tert-butyl(tert-butoxycarbonylamino)(4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-ylamino)methylenecarbamate;-   299)    N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-1H-indazole-5-carboxamide;-   300)    N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-3-methyl-1H-pyrazole-5-carboxamide;-   301)    1-amino-9b-(furane-2-carboxamido)-7-methoxy-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-4b-yl    furane-2-carboxylate;-   302)    N-(4b-hydroxy-7,8-dimethyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)nicotinamide;-   303)    N-(4b-hydroxy-7,8-dimethyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl-1H-pyrrole-2-carboxamide;-   304)    N-(6-ethyl-4b-hydroxy-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-1H-pyrrole-2-carboxamide;-   305)    N-(6-ethyl-4b-hydroxy-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)furane-2-carboxamide;-   306)    N-(8-chloro-4b-hydroxy-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)quinoline-4-carboxamide;    and-   307)    N-(8-chloro-4b-hydroxy-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)tetrahydrofurane-2-carboxamide.    -   Preferred examples of the indanone derivative represented by        Chemical Formula 1 are as follows: Compounds 29), 45)˜47),        49)˜63), 65)˜67), 70)˜75), 77)˜78), and 87)˜307).    -   More preferred examples of the indanone derivative represented        by Chemical Formula include: Compounds 196)˜207), 212)˜217),        228), 231)˜235), 237)˜238), and 241)˜307).

The indanone derivatives, represented by Chemical Formula 1, accordingto the present invention may be used in the form of pharmaceuticalacceptable salts. Useful are acid addition salts formed withpharmaceutically acceptable free acids. As used herein, the term“pharmaceutically acceptable salt” refers to any organic or inorganicsalt of the base compounds of Chemical Formula 1, not exhibiting a sideeffect in which the beneficial activity of the base compounds ofChemical Formula 1 is degraded when it is present at a concentrationcausing no toxicity and harm in the body. The free acids may beinorganic or organic. Examples of useful inorganic free acids includehydrochloric acid, bromic acid, nitric acid, sulfuric acid, perchloricacid and phosphoric acid. As organic acids, citric acid, acetic acid,lactic acid, maleic acid, fumaric acid, gluconic acid, methane sulfonicacid, gluconic acid, succinic acid, tartaric acid, galacturonic acid,embonic acid, glutamic acid, aspartic acid, oxalic acid, (D)- or(L)-malic acid, maleic acid, methanesulfonic acid, ethanesulfonic acid,4-toluenesulfonic acid, salicylic acid, benzoic acid, or malonic acidmay be used. The pharmaceutically acceptable salts may include alkalimetal salts (sodium salt, potassium salt, etc.) and alkaline earth metalsalts (calcium salt, magnesium salt, etc.). Acid addition salts usefulin the present invention include, but are not limited to, acetate,aspartate, benzoate, besylate, bicarbonate/carbonate, bisulfate/sulfate,borate, camsylate, citrate, edisylate, esylate, formate, fumarate,gluceptate, gluconate, glucuronate, hexafluorophosphate, hibenzate,hydrochloride/chloride, hydrobromide/bromide, hydroiodide/iodide,isethionate, lactate, malate, maleate, malonate, mesylate,methylsulfate, naphthylate, 2-napsylate, nicotinate, nitrate, orotate,oxalate, palmitate, pamoate, phosphate/hydrogen phosphate/dihydrogenphosphate, saccharate, stearate, succinate, tartrate, tosylate,trifluoroacetate, aluminum, arginine, benzathine, calcium, choline,diethylamine, diolamine, glycine, lysine, magnesium, meglumine, alamine,potassium, sodium, tromethamine, and zinc salt, with hydrochloride ortrifluoroacetate being preferred. Addition salts according to thepresent invention may be prepared by typical methods. For example, theymay be prepared by dissolving the compound of Chemical Formula 1 in anorganic solvent, such as methanol, ethanol, acetone, methylene chloride,or acetonitrile, and adding an excess of organic acids or an excess ofaqueous inorganic acid solutions so as to precipitate or crystallizesalts. These addition salts may be obtained by precipitation orcrystallization, or by evaporating the solvent or excess acid and dryingor suction-filtering the precipitated salt.

Also, pharmaceutically acceptable metal salts formed with bases may fallwithin the range of pharmaceutically acceptable salts of the compound ofthe present invention. Examples of the metal salts useful in the presentinvention include alkali metal salts and alkaline earth metal salts. Byway of example, the compound of the present invention may be dissolvedin excess alkali metal hydroxide or alkaline earth metal hydroxide inwater, and, after the filtration of the solution to remove non-dissolvedcompound salts, the filtrate may be dried to afford the pharmaceuticallyacceptable salts of the compound of the present invention. Suitable foruse in pharmaceutics are sodium, potassium or calcium salts.Corresponding silver salts may be obtained by reacting the alkali metalor alkaline earth metal salts with suitable silver salt (e.g., silvernitrate).

Not only the indanone derivatives of compound of Chemical Formula 1 andpharmaceutically acceptable salts thereof, but also solvates, hydratesand isomers prepared therefrom, if having the same effect, are withinthe scope of the present invention.

Also, the present invention is concerned with a method for thepreparation of the indanone derivative according to the presentinvention. In one embodiment, the method comprises acylating oralkylating the compound of Chemical Formula 1 with a base in a solventto afford a compound of Chemical Formula 1a (step 1), as illustrated inthe following Reaction Scheme 1:

wherein,

the compound of Chemical Formula 1a is a derivative of the compound ofChemical Formula 1, a pharmaceutically acceptable salt thereof, or anenantiomer thereof,

A¹, A², A³, A⁴, D, E, G¹, G², G³, G⁴, X, Y, and Z are as defined inChemical Formula 1, respectively,

J and L are, independently or optionally, the same as A¹, A², A³, A⁴, D,E, G¹, G², G³, or G⁴.

As the solvent useful in Reaction Scheme 1, diisopropylether,diethylether, dioxane, tetrahydrofurane (THF), dimethylformamide (DMF),dimethylacetamide (DMA), dimethylsulfoxide (DMSO), methylene chloride(MC), chlorobenzene, toluene, or benzene may be employed.

The base used in this reaction may be pyridine (PPTs), 4-dimethylaminopyridine, trimethylamine, or ethylamine.

In another embodiment, the method comprises:

reacting the compound of Chemical Formula 1 with thionyl chloride oroxalic chloride in the presence of a base in a solvent and then withammonia to give a compound of Chemical Formula 2 (step 1); and

acylating or alkylating the compound of Chemical Formula 2 in thepresence of a base in a solvent to afford a compound of Chemical Formula1b (step 2), as illustrated in the following Reaction Scheme 2:

wherein,

the compound of Chemical Formula 1b is a derivative of the compound ofChemical Formula 1, a pharmaceutically acceptable salt thereof, or anenantiomer thereof,

A¹, A², A³, A⁴, D, E, G¹, G², G³, G⁴, X, Y, and Z are as defined inChemical Formula 1, respectively,

J and L are, independently or optionally, the same as A¹, A², A³, A⁴, D,E, G¹, G², G³, or G⁴.

The solvents used in steps 1 and 2 in Reaction Scheme 2 of this methodmay be, independently, selected from the group consisting ofdiisopropylether, diethylether, dioxane, tetrahydrofurane (THF),dimethylformamide (DMF), dimethylacetamide (DMA), dimethylsulfoxide(DMSO), methylene chloride (MC), chlorobenzene, toluene, and benzene.

As the base for the acylating or alkylating reaction in this method,pyridine (PPTs), trimethylamine, ethylamine, or triphosgene may be used.

Also contemplated in accordance with an aspect of the present inventionis a pharmaceutical composition of the prevention or treatment of aviral disease, comprising an indanone derivative represented by ChemicalFormula 1, a pharmaceutically acceptable salt thereof, or an enantiomerthereof as an active ingredient.

The viral disease that the pharmaceutical composition of the presentinvention targets is a disease caused by picornaviruses includingcoxsackie-, entero-, polio-, and rhinoviruses. Examples of the viraldisease include poliomyelitis, paralysis, acute hemorrhagicconjunctivitis, viral meningitis, hand-foot-and-mouth disease, vesiculardisease, hepatitis A, myositis, myocarditis, pancreatitis, epidemicmyalgia, encephalitis, cold, herpangina, and foot-and-mouth disease.

Having excellent antiviral activity against picornaviruses such ascoxsackie-, entero-, echo-, polio- and rhinoviruses as well asexhibiting low cytotoxicity, the indanone derivative of Chemical Formula1 can be useful as an active ingredient of a pharmaceutical compositionfor the prevention or treatment of various viral diseases includingpoliomyelitis, paralysis, acute hemorrhagic conjunctivitis, viralmeningitis, hand-foot-and-mouth disease, vesicular disease, hepatitis A,myositis, myocarditis, pancreatitis, diabetes, epidemic myalgia,encephalitis, cold, herpangina, foot-and-mouth disease, asthma, chronicobstructive pulmonary disease, pneumonia, sinusitis, and otitis media.

Clinically, the compound of the present invention may be administered inthe form of various formulations. For this, the compound is usuallyformulated in combination with a diluent or excipient, such as a filler,a thickening agent, a binder, a wetting agent, a disintegrant, asurfactant, etc.

Solid preparations intended for oral administration of the compound ofthe present invention may take the form of tablets, pills, powders,granules, capsules, troches, and the like. These solid preparations areformulated in combination with at least one excipient such as starch,calcium carbonate, sucrose, lactose, or gelatine. In addition to asimple excipient, a lubricant such as magnesium stearate, talc, or thelike may also be added. Liquid preparations intended for oraladministration include suspensions, internal use solutions, emulsion,syrups, and the like. In addition to a simple diluent such as water orliquid paraffin, various excipients, such as wetting agents, sweeteningagents, aromatics, preservatives, and the like may be contained in theliquid preparations for the oral administration of the compound of thepresent invention.

Also, the compound of the present invention may be in a parenteraldosage form such as sterile aqueous solutions, non-aqueous solvents,suspensions, emulsions, lyophilizates, suppositories, and the like.Propylene glycol, polyethylene glycol, vegetable oils such as olive oil,and esters such as ethyl oleate may be suitable for the non-aqueoussolvents and suspensions. The basic materials of suppositories includeWitepsol, macrogol, Tween 61, cacao butter, laurin butter, andglycerogelatin.

The compound of the present invention is administered in atherapeutically effective amount. The effective dose of the compound ofthe present invention varies depending on various factors including apatient's age, weight, sex, and health condition, the route ofadministration, and the severity of disease. Typically, the compound ofthe present invention may be administered at a daily dose of from 0.001to 100 mg/kg, and preferably at a daily dose of from 0.01 to 35 mg/kg.For an adult with a weight of 70 kg, the dose of the compound of thepresent invention may typically range from 0.07 to 7,000 mg/day, andpreferably from 0.7 to 2,500 mg/day. The formulations of the compoundmay be administered in a single dose or may be divided into multipledoses at regular intervals of time according to the instructions of aphysician or pharmacist who is responsible for monitoring or observingthe administration of the drug.

MODE FOR INVENTION

A better understanding of the present invention may be obtained throughthe following examples which are set forth to illustrate, but are not tobe construed as limiting the present invention.

<Example 1>4b,9b-Dihydroxy-7-methyl-4bH-benzo[d]indeno[1,2-b]furan-10(9bH)-one

Ninhydrin (6.00 g, 33.6 mmol and m-cresol (3.78 ml, 33.6 mmol weredissolved in acetic acid (30 ml) and heated for 3 hrs under reflux.After cooling, the precipitate thus formed was washed with acetic acidand water in that order to afford the title compound as a white solid.7.55 g (83%).

mp: 145-147° C.

¹H-NMR (300 MHz, CDCl₃) δ 2.26 (s, 3H, CH₃) 6.63 (s, 1H, ArH) 6.75 (d,J=7.8 Hz, 1H, ArH) 7.34 (d, J=7.8 Hz, 1H, ArH) 7.54 (t, J=7.5 Hz, 1H,ArH) 7.74-7.81 (m, 2H, ArH) 7.97-8.00 (d, J=7.8 Hz, 1H, ArH). MS (EI):268

<Example 2>7-Methyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furane-4b,9b-diyldiacetate

4b,9b-dihydroxy-7-methyl-4bH-benzo[d]indeno[1,2-b]furan-10(9bH)-one(1.00 g, 3.7 mmol) was completely dissolved in anhydrous dichloromethane(50 ml). This solution was added with anhydrous acetic acid (0.7 ml, 7.4mmol), pyridine (0.3 ml, 3.7 mmol), and 4-dimethyl aminopyridine (0.1g), and stirred at room temperature for 3 hrs. After the reactionmixture was extracted with dichloromethane, the organic layer wasconcentrated and purified using column chromatography(ethylacetate:hexane=1:8) to afford the title compound. 0.04 g (3%).

mp: 167-169° C.

¹H-NMR (300 MHz, CDCl₃) δ 2.15 (s, 3H, OAc) 2.16 (s, 3H, OAc) 2.30 (s,3H, CH₃) 6.69 (s, 1H, ArH) 6.88 (d, J=7.8 Hz, 1H, ArH) 7.47 (d, J=7.7Hz, 1H, ArH) 7.58 (t, J=7.4 Hz, 1H, ArH) 7.75-7.84 (m, 2H, ArH) 8.14 (d,J=7.7 Hz, 1H, ArH). MS (EI): 352.

<Example 3> Ethyl2-(4b,9b-dihydroxy-6-methoxy-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furane-8-yl)acetate

Ninhydrin (2.54 g, 14.2 mmol) andethyl-2-(4-hydroxy-3-methoxyphenyl)acetate (3.00 g, 14.2 mmol) weredissolved in acetic acid (15 ml) and heated for 21 hrs under reflux,followed by extraction with ethylacetate. The concentrate was purifiedusing column chromatography (ethylacetate:hexane=1:1) to afford thetitle compound. 1.46 g (29%).

mp: 133-136° C.

¹H-NMR (300 MHz, CDCl₃) δ 1.20 (t, J=7.2 Hz, 3H, CH₃) 3.56 (s, 2H, CH₂)3.82 (s, 3H OCH₃) 4.11-4.18 (q, J=7.2 Hz, 14.4H, 2H, OCH₂) 6.89 (s, 1H,ArH) 7.12 (s, 1H, ArH) 7.56-8.14 (m, 4H, ArH). MS (EI): 370.

<Example 4>4b,9b-dihydroxy-7,8-dimethyl-4bH-benzo[d]indeno[1,2-b]furan-10(9bH)-one

Ninhydrin (4.37 g, 24.5 mmol) and 3,4-dimethylphenol (3.00 g, 24.5 mmol)were dissolved in acetic acid (15 ml) and heated for 23 hrs underreflux. After cooling, the precipitate thus formed was washed withacetic acid and water in that order to afford the title compound as awhite solid. 5.43 g (78%).

mp: 198-200° C.

¹H-NMR (300 MHz, CDCl₃) δ 2.15 (m, 6H, CH₃) 6.55 (s, 1H, ArH) 7.22 (s,1H, ArH), 7.70-7.88 (m, 4H, ArH). MS (EI): 282.

<Example 5> 2-Hydroxy-2-(2-hydroxyphenyl)-1H-indene-1,3(2H)-dione

Ninhydrin (1.00 g, 5.6 mmol) and phenol (0.53 g, 5.6 mmol) weredissolved in acetic acid (20 ml) and heated for 23 hrs under reflux. Thereaction mixture was cooled, washed with acetic acid and water, and thenrecrystallized in dichloromethane to afford the title compound as awhite solid. 0.37 g (26%).

mp: 155-159° C.

¹H-NMR (300 MHz, acetone-d₆) δ 5.87 (s, 1H, OH) 6.72 (s, 1H, OH) 6.78(d, J=8.4 Hz, 1H, ArH) 6.95 (t, J=6.6 Hz, 1H, ArH) 7.27 (t, J=6.9 Hz,1H, ArH) 7.48 (d, J=7.3 Hz, 1H, ArH) 7.64 (t, J=7.5 Hz, 1H, ArH) 7.75(d, J=7.8 Hz, 1H, ArH) 7.91 (t, J=13.4 Hz, 1H, ArH) 8.01 (d, J=4.8 Hz,1H, ArH). MS (EI): 254.

<Example 6>2-(5-Fluoro-2-hydroxyphenyl)-2-hydroxy-1H-indene-1,3(2H)-dione

Ninhydrin (1.00 g, 5.6 mmol) and 4-fluoro-phenol (0.63 g, 5.6 mmol) weredissolved in acetic acid (20 ml) and heated for 23 hrs under reflux.After coiling, the precipite thus formed was washed with acetic acid andwater, and recrystallized in dichloromethane to afford a white solid.This was purified using column chromatography (ethylacetate:hexane=1:4)and washed with dichloromethane to afford the title compound. 0.57 g(37%).

mp: 189-193° C.

¹H-NMR (300 MHz, acetone-d₆) δ 5.98 (s, 1H, OH) 6.81 (q, J=9.0 Hz, 4.0Hz, 1H, ArH) 6.88 (s, 1H, OH) 7.06 (dt, J=9.0, 2.7 Hz, 1H, ArH) 7.20(dd, J=7.8 Hz, 3.0 Hz, 1H, ArH) 7.66 (t, J=6.9 Hz, 1H, ArH) 7.77 (d,J=7.8 Hz, 1H, ArH) 7.92 (t, J=7.8 Hz, 1H, ArH) 8.00-8.03 (m, 1H, ArH).MS (EI): 272.

<Example 7>4b,9b-Dihydroxy-7-methoxy-4bH-benzo[d]indeno[1,2-b]furan-10(9bH)-one

3-Methoxyphenol (2.09 g, 16.8 mmol) and ninhydrin (3.00 g, 16.8 mmol)were dissolved in acetic acid (20 ml) and heated for 2 hrs under reflux.Then, the reaction mixture was extracted with ethylacetate and theconcentrated organic layer was purified using column chromatography(ethylacetate:hexane=1:4), followed by recrystallization withethylacetate and hexane to afford the title compound. 1.25 g (26%).

mp: 98-100° C.

¹H-NMR (300 MHz, CDCl₃) δ 3.82 (s, 3H, OCH₃) 6.39 (s, 1H, ArH) 6.52 (d,1H, J=9.0 Hz, ArH) 7.37 (d, 1H, J=9.0 Hz, ArH) 7.57 (t, 1H, J=9.0 Hz,ArH) 7.78-7.81 (m, 2H, ArH) 7.99 (d, J=9.0 Hz, 1H, ArH). MS (EI): 284.

<Example 8>6,7-Dichloro-4b,9b-dihydroxy-4bH-benzo[d]indeno[1,2-b]furan-10(9bH)-one

Ninhydrin (3.00 g, 16.8 mmol) and 2,3-chlorophenol (2.16 g, 16.8 mmol)were dissolved in acetic acid (20 ml) and heated for 28 hrs underreflux. The precipitate thus formed was washed with dichloromethane toafford the title compound as a white solid. 2.35 g (43%).

mp: 142-150° C.

¹H-NMR (300 MHz, CDCl₃) δ 7.06 (d, J=8.1 Hz, 1H, ArH) 7.33 (d, J=8.1 Hz,1H, ArH) 7.61 (t, J=7.5 Hz, 1H, ArH) 7.80-7.88 (m, 2H, ArH) 8.07 (d,J=7.8 Hz, 1H, ArH). MS (EI): 323.

<Example 9>7-Ethyl-4b,9b-dihydroxy-4bH-benzo[d]indeno[1,2-b]furan-10(9bH)-one

Ninhydrin (3.00 g, 16.8 mmol) and m-ethylphenol (2.05 g, 16.8 mmol) weredissolved in acetic acid (20 ml) and heated for 4 hrs under reflux.After cooling, the precipitate thus formed was washed withdichloromethane to afford the title compound as a white solid. 2.80 g(59%).

mp: 168-169° C.

¹H-NMR (300 MHz, CDCl₃) δ 1.15 (t, J=7.8 Hz, 3H, CH₃) 2.53-2.60 (q,J=15.3 Hz, 7.5 Hz, CH₂) 3.93 (s, 1H, OH) 4.75 (s, 1H, OH) 6.68 (s, 1H,ArH) 6.80 (d, J=6.0 Hz, 1H, ArH) 7.38 (d, J=7.8 Hz, 1H, ArH) 7.55 (t,J=7.5 Hz, 1H, ArH) 7.79 (t, J=9.0 Hz, 2H, ArH) 8.00 (d, J=7.8 Hz, 1H,ArH). MS(EI): 282.

<Example 10>4b,9b-Dihydroxy-7-isopropyl-4bH-benzo[d]indeno[1,2-b]furan-10(9bH)-one

Ninhydrin (3.00 g, 16.8 mmol) and m-isopropylphenol (2.29 g, 16.8 mmol)were dissolved in acetic acid (20 ml) and heated for 2 hrs under reflux.After cooling, the precipitate thus formed was washed withdichloromethane to afford the title compound as a white solid. 2.82 g(56%).

mp: 195-198° C.

¹H-NMR (300 MHz, CDCl₃) δ 1.16 (d, J=8.1 Hz, 6H, CH₃) 2.77-2.86 (m, 1H,CH) 4.14 (s, 1H, OH) 4.85 (s, 1H, OH) 6.70 (s, 1H, ArH) 6.82 (d, J=7.8Hz, 1H, ArH) 7.40 (d, J=7.8 Hz, 1H, ArH) 7.54 (t, J=7.8 Hz, 1H, ArH)7.75-7.82 (m, 2H, ArH) 8.00 (d, J=7.8 Hz, 1H, ArH). MS(EI): 296.

<Example 11>7-Isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furane-4b,9b-diyldiacetate

4b,9b-Dihydroxy-7-isopropyl-4bH-benzo[d]indeno[1,2-b]furan-10(9bH)-one(2.00 g, 6.7 mmol) was completely dissolved in anhydroustetrahydrofurane (20 ml), and mixed with anhydrous acetic acid (1.38 g,13.5 mmol), pyridine (0.53 g, 6.7 mmol), 4-dimethyl aminopyridine (0.2g) at room temperature for 12 hrs while stirring. The reaction mixturewas concentrated and extracted many times with dichloromethane, and theconcentrated organic layer was purified using column chromatography(ethylacetate:hexane=1:4) to afford the title compound. 0.27 g (11%).

mp: 138-140° C.

¹H-NMR (300 MHz, CDCl₃) δ 1.18 (d, J=6.9 Hz, 6H, CH₃) 2.14 (s, 3H, OAc)2.16 (s, 3H, OAc) 2.83-2.87 (m, 1H, CH) 6.75 (s, 1H, ArH) 6.94 (d, J=7.8Hz, 1H, ArH) 7.51 (d, J=7.5 Hz, 1H, ArH) 7.59 (t, J=7.5 Hz, 1H, ArH)7.75-7.85 (m, 2H, ArH) 8.16 (d, J=7.8 Hz, 1H, ArH). MS(EI): 380

<Example 12>4b,9b-Dihydroxy-8-methoxy-4bH-benzo[d]indeno[1,2-b]furan-10(9bH)-one

Ninhydrin (3.00 g, 16.8 mmol) and p-methoxyphenol (2.09 g, 16.8 mmol)were dissolved in acetic acid (20 ml) and heated for 6 hrs under reflux.After cooling, the precipitate thus formed was washed with acetic acidand water in that order to afford the title compound as a yellow solid.4.00 g (83%).

mp: 186-189° C.

¹H-NMR (300 MHz, CDCl₃) δ 3.72 (s, 3H, OCH₃) 6.59 (d, J=8.8 Hz, 1H, ArH)6.70 (dd, J=8.8 Hz, 1H, ArH) 6.97 (d, J=2.8 Hz, 1H, ArH) 7.43 (t, J=7.9Hz, 1H, ArH) 7.64-7.71 (m, 2H, ArH) 7.84-7.87 (d, J=7.7 Hz, 1H, ArH).MS(EI): 284.

<Example 13>4b,9b-Dihydroxy-6-phenyl-4bH-benzo[d]indeno[1,2-b]furan-10(9bH)-one

Ninhydrin (3.00 g, 16.8 mmol) and m-phenylphenol (2.86 g, 16.8 mmol)were added to acetic acid (20 ml) and heated for 20 hrs under reflux.After the removal of the solvent by concentration in a vacuum, theconcentrate was extracted many times with dichloromethane. Theconcentrated organic layer was crystallized with dichlorometan andhexane to afford the title compound as a white solid. 4.10 g (73%).

mp: 182-183° C.

¹H-NMR (300 MHz, CDCl₃) δ 7.03 (t, J=6.0 Hz, 1H, ArH) 7.30-7.41 (m, 1H,ArH) 7.42-7.48 (m, 4H, ArH) 7.54 (t, J=7.8 Hz, 1H, ArH) 7.63 (d, J=8.4Hz, 2H, ArH) 7.76-7.81 (m, 2H, ArH) 8.01 (d, J=8.1 Hz, 1H, ArH). MS(EI):330.

<Example 14>4b,9b-Dihydroxy-8-nitro-4bH-benzo[d]indeno[1,2-b]furan-10(9bH)-one

Ninhydrin (3.00 g, 16.8 mmol) and 4-nitrophenol (2.34 g, 16.8 mmol) wereadded to acetic acid (20 ml) and heated for 5 hrs under reflux. Thereaction mixture was extracted many times with dichloromethane and theconcentrated organic layer was purified using column chromatography(ethylacetate:hexane=1:3) to afford the title compound. White. 0.80 g(16%).

mp: 206-207° C.

¹H-NMR (300 MHz, CDCl₃) δ 6.94 (d, J=9.0 Hz, 1H, ArH) 7.63 (t, J=7.8 Hz,1H, ArH) 7.80-7.90 (m, 2H, ArH) 8.03 (d, J=7.8 Hz, 1H, ArH) 8.24 (d,J=9.0 Hz, 1H, ArH) 8.42 (d, J=2.4 Hz, 1H, ArH). MS(EI): 299.

<Example 15> 4b,11b-Dihydroxy-4bH-indeno[1,2-b]naphtho[2,3-d]furan-12(11bH)-one

Ninhydrin (1.00 g, 5.61 mmol) and 2-naphthol (0.81 g, 5.61 mmol) weredissolved in acetic acid (20 ml) and heated for 6 hrs under reflux.After cooling, the precipitate thus formed was washed with acetic acidand water in that order to afford the title compound as a white solid.1.31 g (77%).

mp: 220-221° C.

¹H-NMR (300 MHz, CDCl₃) δ 7.06 (d, J=8.7 Hz, 1H, ArH) 7.37 (t, J=7.5 Hz,1H, ArH) 7.52-7.62 (m, 2H, ArH) 7.76-7.83 (m, 4H, ArH) 8.04 (d, J=7.8Hz, 1H, ArH) 8.38 (d, J=8.4 Hz, 1H, ArH). MS(EI): 304.

<Example 16> 6b,11b-Dihydroxy-6bH-indeno[1,2-b]naphtho[2,1-d]furan-7(11bH)-one

Ninhydrin (1.00 g, 5.61 mmol) and 1-naphthol (0.81 g, 5.61 mmol) wereadded to acetic acid (20 ml) and heated for 7 hrs under reflux. Aftercooling the reaction mixture, the precipitate thus formed was washedwith acetic acid and water in that order to afford the title compound asa white solid. 0.96 g (56%).

mp: 216-218° C.

¹H-NMR (300 MHz, CDCl₃) δ 7.43-7.57 (m, 5H, ArH) 7.75-7.83 (m, 3H, ArH)8.03-8.12 (m, 2H, ArH). MS(EI): 304.

<Example 17>4b,9b-Dihydroxy-8-propyl-4bH-benzo[d]indeno[1,2-b]furan-10(9bH)-one

Ninhydrin (1.00 g, 5.61 mmol) and p-propylphenol (0.76 g, 5.61 mmol)were added to acetic acid (20 ml) and heated for 16 hrs under reflux.The reaction mixture was extracted many times with dichloromethane, andthe concentrated organic layer was purified using column chromatography(ethylacetate:hexane=1:3 to 1:1) to afford the title compound. 1.10 g(66%).

mp: 126-127° C.

¹H-NMR (300 MHz, CDCl₃) δ 0.83-0.90 (t, J=7.4 Hz, 3H, CH₃) 1.46-1.57 (m,2H, CH₂) 2.45 (t, J=7.8 Hz, 2H, CH₂) 6.74 (d, J=8.4 Hz, 1H, ArH) 7.08(dd, J=1.8, 8.4 Hz, 1H, ArH) 7.31 (s, 1H, ArH) 7.55 (t, J=7.8 Hz, 1H,ArH) 7.77-7.82 (m, 2H, ArH) 8.00 (d, J=7.5 Hz, 1H, ArH). MS(EI): 296.

<Example 18>8-Ethyl-4b,9b-dihydroxy-4bH-benzo[d]indeno[1,2-b]furan-10(9bH)-one

Ninhydrin (1.00 g, 5.61 mmol) and p-ethylphenol (0.68 g, 5.61 mmol) weredissolved in acetic acid (20 ml) and heated for 15 hrs under reflux.After cooling the reaction mixture for 12 hrs, the precipitate thusformed was washed with acetic acid and water in that order to afford thetitle compound as a yellowish white solid. 1.10 g (69%).

mp: 157-159° C.

¹H-NMR (300 MHz, CDCl₃) δ 1.16 (t, J=7.4 Hz, 3H, CH₃) 2.50-2.61 (q,J=7.6 Hz, 2H, CH₂) 3H, OAc) 6.74 (d, J=8.4 Hz, 1H, ArH) 7.10 (d, J=8.4Hz, 1H, ArH) 7.33 (s, 1H, ArH) 7.54 (t, J=8.0 Hz, 1H, ArH) 7.76-7.83 (m,2H, ArH) 8.00 (d, J=7.6 Hz, 1H, ArH). MS(EI): 282.

<Example 19>8-sec-Butyl-4b,9b-dihydroxy-4bH-benzo[d]indeno[1,2-b]furan-10(9bH)-one

Binhydrin (1.00 g, 5.61 mmol) and p-sec-butylphenol (0.84 g, 5.61 mmol)were added to acetic acid (20 ml) and heated for 20 hrs under reflux.The reaction mixture was extracted many times with dichloromethane, andthe concentrated organic layer was purified using column chromatography(ethylacetate:hexane=1:4 to 1:2) to afford the title compound. 0.80 g(46%).

mp: 134-136° C.

¹H-NMR (300 MHz, CDCl₃) δ 0.77 (t, J=7.2 Hz, 3H, CH₃) 1.16 (d, J=6.9 Hz,3H, CH₃) 1.31-1.43 (m, 2H, CH₂) 2.49-2.56 (m, 1H, CH) 6.75 (d, J=8.1 Hz,1H, ArH) 7.09 (d, J=8.4 Hz, 1H, ArH) 7.33 (s, 1H, ArH) 7.59 (m, 1H, ArH)7.79-7.83 (m, 2H, ArH) 8.00 (d, J=7.5 Hz, 1H, ArH). MS(EI): 310.

<Example 20>8-tert-Butyl-4b,9b-dihydroxy-4bH-benzo[d]indeno[1,2-b]furan-10(9bH)-one

Ninhydrin (1.00 g, 5.61 mmol) and p-tert-butylphenol (0.84 g, 5.61 mmol)were added to acetic acid (20 ml) and heated for 16 hrs under reflux.The reaction mixture was extracted many times with dichloromethane, andthe concentrated organic layer was purified using column chromatography(ethylacetate:hexane=1:2) to afford the title compound. 0.60 g (34%).

mp: 187-188° C.

¹H-NMR (300 MHz, CDCl₃) δ 1.22 (s, 9H, CH₃) 6.78 (d, J=8.4 Hz, 1H, ArH)7.27-7.28 (m, 1H, ArH) 7.46 (d, J=2.1 Hz, 1H, ArH) 7.57 (t, J=7.5 Hz,1H, ArH) 7.79-7.84 (t, J=7.5 Hz, 2H, ArH) 8.00 (d, J=2.1 Hz, 1H, ArH).MS(EI): 310.

<Example 21>6-tert-Butyl-4b,9b-dihydroxy-4bH-benzo[d]indeno[1,2-b]furan-10(9bH)-one

Ninhydrin (0.60 g, 5.6 mmol) and 2-tert-butylphenol (0.84 g, 5.6 mmol)were dissolved in acetic acid (10 ml) and heated for 7 hrs under reflux.After cooling the reaction mixture, the precipitate thus formed waswashed with acetic acid and water in that order to afford the titlecompound as a white solid. 1.09 g (62%).

mp: 148-152° C.

¹H-NMR (300 MHz, CDCl₃) δ 1.35 (s, 9H, CH₃) 6.93 (t, J=7.8 Hz, 1H, ArH)7.23-7.37 (m, 2H, ArH) 7.57 (t, J=7.4 Hz, 1H, ArH) 7.80 (t, J=7.8 Hz,2H, ArH) 8.05 (d, J=7.8 Hz, 1H, ArH). MS(EI): 310.

<Example 22>4b,9b-Dihydroxy-7,8,9-trimethyl-4bH-benzo[d]indeno[1,2-b]furan-10(9bH)-one

Ninhydrin (1.00 g, 5.61 mmol) and 3,4,5-trimethylphenol (0.76 g, 5.61mmol) were dissolved in acetic acid (20 ml) and heated for 16 hrs underreflux. The reaction mixture was extracted many times withdichloromethane and the concentrated organic layer was purified usingcolumn chromatography (ethylacetate:hexane=1:4 to 1:2) to afford thetitle compound. 1.01 g (60%).

mp: 212-214° C.

¹H-NMR (300 MHz, CDCl₃) δ 2.05 (s, 3H, CH₃) 2.19 (s, 3H, CH₃) 2.44 (s,3H, CH₃) 6.53 (s, 1H, ArH) 7.53 (t, J=6.9 Hz, 1H, ArH) 7.74-7.80 (m, 2H,ArH) 7.96 (d, J=7.2 Hz, 1H, ArH). MS(EI): 296.

<Example 23>4b,9b-Dihydroxy-8-tert-pentyl-4bH-benzo[d]indeno[1,2-b]furan-10(9bH)-one

Ninhydrin (1.00 g, 5.61 mmol) and 4-tert-pentylphenol (0.92 g, 5.61mmol) were dissolved in acetic acid (20 ml) and heated for 32 hrs underreflux. The reaction mixture was extracted many times withdichloromethane, and the concentrated organic layer was purified usingcolumn chromatography (ethylacetate:hexane=1:4) to afford the titlecompound. 1.28 g (70%).

mp: 175-176° C.

¹H-NMR (300 MHz, CDCl₃) δ 0.63 (t, J=7.5 Hz, 3H, CH₃) 1.22 (s, 6H, CH₃)1.53-1.60 (q, J=15.0, 7.5 Hz, 2H, CH₂) 6.78 (d, J=8.4 Hz, 1H, ArH) 7.28(m, 1H, ArH 7.46 (d, J=2.1 Hz, 1H, ArH) 7.57 (t, J=7.5 Hz, 1H, ArH)7.79-7.84 (t, J=7.5 Hz, 2H, ArH) 8.00 (d, J=6.90 Hz, 1H, ArH). MS(EI):324.

<Example 24>6,8-di-tert-Butyl-4b,9b-dihydroxy-4bH-benzo[d]indeno[1,2-b]furan-10(9bH)-one

Ninhydrin (1.00 g, 5.61 mmol) and 2,4-tert-butyl-phenol (1.16 g, 5.61mmol) were dissolved in acetic acid (20 ml) and heated for 16 hrs underreflux. The reaction mixture was extracted many times withdichloromethane, and the organic layer was dried, filtered andconcentrated in a vacuum. The solid thus formed was washed with hexaneto afford the title compound. 0.60 g (34%).

mp: 200-203° C.

¹H-NMR (300 MHz, CDCl₃) δ 1.25 (s, 9H, CH₃) 1.33 (s, 9H, CH₃) 7.31 (d,J=2.1 Hz, 1H, ArH) 7.35 (d, J=2.1 Hz, 1H, ArH) 7.55 (t, J=9.0 Hz, 1H,ArH) 7.76-7.81 (m, 2H, ArH) 8.01 (d, J=7.8 Hz, 1H, ArH). MS(EI): 366.

<Example 25>6,8-di-tert-Butyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furane-4b,9b-diyldiacetate

6,8-di-tert-Butyl-4b,9b-dihydroxy-4bH-benzo[d]indeno[1,2-b]furan-10(9bH)-one(0.60 g, 0.60 mmol) was completedly dissolved in anhydroustetrahydrofurane (20 ml), and reacted overnight with anhydrous aceticacid (0.33 g, 3.28 mmol), pyridine (0.13 g, 1.64 mmol), and 4-dimethylaminopyridine (0.06 g) at room temperature while stirring. The reactionmixture was extracted many times with dichloromethane, and theconcentrated organic layer was purified using column chromatography(ethylacetate:hexane=1:3) to afford the title compound. 0.61 g (61%).

mp: 242-247° C.

¹H-NMR (300 MHz, CDCl₃) δ 1.29 (s, 18H, CH₃) 2.13 (s, 3H, OAc) 2.18 (s,3H, OAc) 7.31 (d, J=2.1 Hz, 1H, ArH) 7.43 (d, J=1.8 Hz, 1H, ArH) 7.57(t, J=7.5 Hz, 1H, ArH) 7.73-7.84 (m, 2H, ArH) 8.19 (d, J=7.8 Hz, 1H,ArH). MS(EI): 450.

<Example 26>4b,9b-Dihydroxy-8-nonyl-4bH-benzo[d]indeno[1,2-b]furan-10(9bH)-one

Ninhydrin (1.00 g, 5.61 mmol) and nonylphenol (1.23 g, 5.61 mmol) weredissolved in acetic acid (20 ml) and heated for 20 hrs under reflux. Thereaction mixture was extracted many times with dichloromethane, and theconcentrated organic layer was purified using column chromatography(ethylacetate:hexane=1:4) to afford the title compound. 1.01 g (47%).

mp: 108-110° C.

¹H-NMR (300 MHz, CDCl₃) δ 0.50-1.28 (m, 16H, CH₂) 2.09 (s, 3H, CH₃) 6.76(d, J=8.4 Hz, 1H, ArH) 7.38-7.44 (m, 1H, ArH) 7.56 (t, J=7.8 Hz, 1H,ArH) 7.81 (t, J=7.5 Hz, 2H, ArH) 8.01 (t, J=7.5 Hz, 1H, ArH). MS(EI):380.

<Example 27>4b,9b-Dihydroxy-8-pentadecyl-4bH-benzo[d]indeno[1,2-b]furan-10(9bH)-one

Ninhydrin (1.00 g, 5.61 mmol) and 2-pentadecylphenol (1.70 g, 5.61 mmol)were dissolved in acetic acid (20 ml) and heated for 20 hrs underreflux. The reaction mixture was extracted many times withdichloromethane, and the concentrated organic layer was purified usingcolumn chromatography (ethylacetate:hexane=1:4) to afford the titlecompound. 1.01 g (37%).

mp: 105-110° C.

¹H-NMR (300 MHz, CDCl₃) δ 0.87 (t, J=6.3 Hz, 3H, CH₃) 1.24 (s, 24H, CH₂)1.52-1.54 (m, 2H, CH₂), 2.53 (t, J=7.6 Hz, 2H, CH₂) 6.68 (s, 1H, ArH)6.81 (d, J=7.6 Hz, 1H, ArH) 7.40 (d, J=7.8 Hz, 1H, ArH) 7.58 (t, J=7.0Hz, 1H, ArH) 7.83 (t, J=6.80 Hz, 2H, ArH) 8.02 (d, J=8.4 Hz, 1H, ArH).MS(EI): 464.

<Example 28>6,8-Bis-(1,1-dimethyl-propyl)-4b,9b-dihydroxy-4b,9b-dihydro-5-oxa-indeno[2,1-a]inden-10-one

Ninhydrin (1.00 g, 5.6 mmol) and 2,4-di-tert-pentylphenol (1.31 g, 5.6mmol) were added to acetic acid (20 ml) and heated for 16 hrs underreflux. The reaction mixture was extracted many times withdichloromethane, and the concentrated organic layer was purified usingcolumn chromatography (ethylacetate:hexane=1:4) to afford the titlecompound. 1.28 g (58%).

mp: 195-222° C.

¹H-NMR (300 MHz, CD₃OD) δ 0.44 (t, J=7.5 Hz, 3H, CH₃) 0.62 (t, J=7.5 Hz,3H, CH₃) 1.23 (s, 9H, CH₃) 1.56 (s, 3H, CH₃) 1.58-1.63 (q, J=15.0 Hz,7.5 Hz, 2H, CH₂) 1.77-1.85 (m, 2H, CH₂) 7.11 (s, 1H, ArH) 7.31 (s, 1H,ArH) 7.57 (t, J=7.8 Hz, 1H, ArH) 7.74 (d, J=7.8 Hz, 1H, ArH) 7.81 (t,J=8.4 Hz, 1H, ArH) 7.96 (d, J=7.8 Hz, 1H, ArH). MS(EI): 394.

<Example 29> Isopropyl4b,9b-dihydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-1-ylcarbamate

To a solution of4b,9b-dihydroxy-1-isocyanato-7-isopropyl-4bH-benzo[d]indeno[1,2-b]furan-10(9bH)-one(70 mg, 0.2 mmol) in anhydrous tetrahydrofurane was dropwide added 2Mammonia (0.21 ml in isopropyl alcohol). The reaction mixture was heatedfor 4 hrs under reflux and concentrated in a vacuum, followed bypurification using column chromatography (ethylacetate:hexane=1:4) toafford the title compound. 30 mg (38%).

mp: 200-202° C.

¹H-NMR (300 MHz, CDCl₃) δ 1.16 (dd, J=6.9, 1.8 Hz, 6H, CH₃) 1.27-1.34(m, 6H, CH₃) 2.78-2.87 (m, 1H, CH) 3.95 (s, 1H, OH) 4.77 (s, 1H, OH)4.96-5.05 (m, 1H, CH) 6.71 (s, 1H, ArH) 6.84 (d, J=8.1 Hz, 1H, ArH) 7.42(d, J=8.1 Hz, 1H, ArH) 7.53 (d, J=7.2 Hz, 1H, ArH) 7.72 (t, J=8.1 Hz,1H, ArH) 8.27 (d, J=8.4 Hz, 1H, ArH) 9.29 (s, 1H, NH). MS(EI): 397.

<Example 30> 2,6′-Dihydroxy-2′,3′-dihydro-1′H-[2,5′]biindenyl-1,3-dione

To a solution of ninhydrin (1.00 g, 5.61 mmol) in acetic acid (20 ml)was added 1-(3-hydroxy-phenyl)-ethanone (0.75 g, 5.61 mmol), followed byheating for 3 hrs at 110° C. The reaction mixture was extracted manytimes with dichloromethane, and the concentrated organic layer waspurified using column chromatography (ethylacetate:hexane=1:2) to affordthe title compound. White. 1.56 g (94%).

mp: 214-217° C.

¹H-NMR (300 MHz, CDCl₃) δ 1.90-2.08 (m, 2H, CH₂) 2.69-2.82 (m, 4H, CH₂)6.68 (s, 1H, ArH) 7.28 (d, J=12.0 Hz, 1H, ArH) 7.54 (t, J=7.2 Hz, 1H,ArH) 7.75-7.81 (m, 2H, ArH) 7.99 (d, J=7.5 Hz, 1H, ArH). MS(EI): 294.

<Example 31>6b,11b-Dihydroxy-1,2,3,4,6b,11b-hexahydro-12-oxa-benzo[4,5]pentaleno[2,1-a]naphthalen-7-one

To a solution of ninhydrin (1.00 g, 5.61 mmol) in acetic acid (20 ml)was added 5,6,7,8-tetrahydro-naphthalen-1-ol (0.83 g, 5.61 mmol),followed by heating for 3 hrs at 110° C. After cooling, the precipitatethus formed was filtered to afford the title compound as a white solid.1.48 g (83%).

mp: 252-254° C.

¹H-NMR (300 MHz, CDCl₃) δ 1.72-1.81 (m, 4H, CH₂) 2.58-2.67 (m, 4H, CH₂)6.71 (d, J=7.8 Hz, 1H, ArH) 7.21 (d, J=7.8 Hz, 1H, ArH) 7.56 (t, J=8.4Hz, 1H, ArH) 7.58-7.83 (m, 2H, ArH) 8.02 (d, J=7.5 Hz, 1H, ArH). MS(EI):308.

<Example 32>4b,9b-Dihydroxy-7-isopropyl-2-methoxy-4b,9b-dihydro-5-oxa-indeno[2,1-a]inden-10-one

Isopropyl phenol (0.065 g, 0.48 mmol was added to a solution of5-methoxy-ninhydrin (0.10 g, 0.48 mmol in acetic acid (20 ml) and heatedfor 15 hrs at 110° C. The reaction mixture was extracted with many timeswith ethylacetate, and the concentrated organic layer was purified usingcolumn chromatography (ethylacetate:hexane=1:4) to afford the titlecompound. White. 0.12 g (77%).

mp: 98-102° C.

¹H-NMR (300 MHz, CDCl₃) δ 1.24 (d, J=6.9 Hz, 6H, CH₃) 2.78-2.85 (s, 1H,CH) 3.98 (s, 3H, OCH₃) 6.71 (s, 1H, ArH) 6.82 (d, J=7.8 Hz, 1H, ArH)7.04-7.08 (dd, J=8.4 Hz, 3.6 Hz, 1H, ArH) 7.39-7.42 (m, 2H, ArH) 7.70(d, J=8.4 Hz, 1H, ArH). MS(EI): 326.

<Example 33>7-Isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-4b,9b-diylbis(2,2-dimethylpropanoate)

To a solution of4b,9b-dihydroxy-7-isopropyl-4bH-benzo[d]indeno[1,2-b]furan-10(9bH)-one(1.00 g, 3.3 mmol in anhydrous tetrahydrofurane were added2,2-dimethyl-propionyl chloride (0.81 g, 6.7 mmol), trimethylamine (0.40g, 4.0 mmol, and 4-dimethylaminopyridine (0.1 g), followed by heatingfor 24 hrs under reflux. The reaction mixture was concentrated in avacuum, and washed many times with dichloromethane. The concentratedorganic layer was purified using column chromatography(ethylacetate:hexane=1:6) to afford the title compound. 0.10 g (6%).

mp: 153-157° C.

¹H-NMR (300 MHz, CDCl₃) δ 1.16-1.26 (m, 24H, CH₃) 2.80-2.89 (m, 1H, CH)6.73 (s, 1H, ArH) 6.93 (d, J=7.8 Hz, 1H, ArH) 7.48 (d, J=7.8 Hz, 1H,ArH) 7.56 (t, J=7.5 Hz, 1H, ArH) 7.75-7.81 (m, 2H, ArH) 8.09 (d, J=7.8Hz, 1H, ArH). MS(EI): 464.

<Example 34>(2E,2′E)-7-Isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-4b,9b-diylbis(3-phenylacrylate)

To a solution of4b,9b-dihydroxy-7-isopropyl-4b,9b-dihydro-5-oxa-indeno[2,1-a]inden-10-one(1.00 g, 3.3 mmol in anhydrous tetrahydrofurane were added,3-phenyl-acryloyl chloride (1.12 g, 6.7 mmol), trimethylamine (0.40 g,4.0 mmol), and 4-dimethylaminopyridine (0.1 g), followed by heating for2 days under reflux. The reaction mixture was concentrated in a vacuumand washed many times with ethylacetate. The concentrated organic layerwas purified using column chromatography (ethylacetate:hexane=1:8 to1:4) to afford the title compound. 0.08 g (9%)

mp: 111-113° C.

¹H-NMR (300 MHz, CDCl₃) δ 1.20 (dd, J=2.7 Hz, 6.8 Hz, 6H, CH₃) 2.88-2.92(m, 1H, CH) 6.37 (d, J=16.0 Hz, 1H, CH) 6.52 (d, J=16.0 Hz, 1H, CH) 6.81(s, 1H, ArH) 6.99 (d, J=7.3 Hz, 1H, ArH) 7.17-7.44 (m, 10H, ArH)7.59-7.91 (m, 6H, CH, ArH) 8.25 (d, J=7.8 z, 1H, ArH). MS(EI): 556.

<Example 35>9b-Hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-4b-ylacrylate

To a solution of4b,9b-dihydroxy-7-isopropyl-4b,9b-dihydro-5-oxa-indeno[2,1-a]inden-10-one(1.00 g, 3.37 mmol in anhydrous tetrahydrofurane were added acryloylchloride (0.61 g, 6.74 mmol, trimethylamine (0.41 g, 4.0 mmol, and4-dimethylaminopyridine (0.1 g), followed by heating for 24 hrs underreflux. The reaction mixture was concentrated in a vacuum and washedmany times with ethylacetate. The concentrated organic layer waspurified using column chromatography (ethylacetate:hexane=1:2 to 1:1) toafford the title compound. 0.02 g (1.7%).

mp: 95-97° C.

¹H-NMR (300 MHz, CDCl₃) δ 1.18 (d, J=2.1 Hz, 7.2 Hz, 6H, CH₃) 2.81-2.87(m, 1H, CH) 3.91 (s, 1H, OH) 5.95 (d, J=7.5 Hz, 2H, CH₂) 6.19-6.28 (m,1H, OH) 6.50 (d, J=12.0 Hz, 1H, ArH) 6.73 (s, 1H, ArH) 6.88 (d, J=8.1Hz, 1H, ArH) 7.52 (d, J=7.8 Hz, 1H, ArH) 7.56 (t, J=7.8 Hz, 1H, ArH)7.80-7.91 (m, 2H, ArH). MS(EI): 350.

<Example 36>9b-Hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-4b-ylfurane-2-carboxylatefurane-2-carboxylic acid

Furane-2-carbonyl chloride (0.88 g, 6.74 mmol, trimethylamine (0.34 g,3.37 mmol, 4-dimethylaminopyridine (0.1 g) were added to a solution of4b,9b-dihydroxy-7-isopropyl-4b,9b-dihydro-5-oxa-indeno[2,1-a]inden-10-one(1.00 g, 3.37 mmol in anhydrous tetrahydrofurane and heated for 24 hrsunder reflux. The reaction mixture was concentrated in a vacuum andwashed many times with ethylacetate. The concentrated organic layer waspurified using column chromatography (ethylacetate:hexane=1:4 to 1:2) toafford the title compound. 0.07 g (5%).

mp: 116-120° C.

¹H-NMR (300 MHz, CDCl₃) δ 1.20 (d, J=2.1 Hz, 6.9 Hz, 6H, CH₃) 2.78-2.88(m, 1H, CH) 4.77 (s, 1H, OH) 6.46-6.48 (s, 1H, CH) 6.71 (s, 1H, ArH)6.90 (d, J=7.2 Hz, 1H, ArH) 7.24 (s, 1H, ArH) 7.50-7.56 (m, 3H, CH, ArH)7.73-7.82 (m, 2H, ArH) 7.93 (d, J=7.8 Hz, 1H, ArH). MS(EI): 390.

<Example 37> Diethyl7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furane-4b,9b-diyldicarbonate

Ethoxy carbonyl chloride (0.81 g, 6.74 mmol, trimethylamine (0.34 g,3.37 mmol, and 4-dimethylaminopyridine (0.1 g) were added to a solutionof4b,9b-dihydroxy-7-isopropyl-4b,9b-dihydro-5-oxa-indeno[2,1-a]inden-10-one(1.00 g, 3.37 mmol) in anhydrous tetrahydrofurane, and heated for 24 hrsunder reflux. The reaction mixture was concentrated in a vacuum andwashed many times with ethylacetate, and the concentrated organic layerwas purified using column chromatography (ethylacetate:hexane=1:4 to1:2) to afford the title compound. 0.03 g (2%).

mp: 150-153° C.

¹H-NMR (300 MHz, CDCl₃) δ 1.16 (dd, J=6.8, 2.8 Hz, 6H, CH₃) 1.20-1.28(m, 6H, CH₃) 2.78-2.85 (m, 1H, CH) 4.14-4.30 (m, 4H, OCH₂) 6.77 (s, 1H,ArH) 6.94 (d, J=7.9 Hz, 1H, ArH) 7.53-7.62 (m, 2H, ArH) 7.76-7.87 (m,2H, ArH) 8.18 (d, J=7.8 Hz, 1H, ArH). MS(EI): 440.

<Example 38> Ethyl9b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-4b-ylcarbonate

Ethoxy carbonyl chloride (0.81 g, 6.74 mmol, trimethylamine (0.34 g,3.37 mmol, and 4-dimethylaminopyridine (0.1 g) were added to a solutionof4b,9b-dihydroxy-7-isopropyl-4b,9b-dihydro-5-oxa-indeno[2,1-a]inden-10-one(1.00 g, 3.37 mmol) in anhydrous tetrahydrofurane, and heated for 24 hrsunder reflux. The reaction mixture was concentrated in a vacuum andwashed many times with ethylacetate, and the concentrated organic layerwas purified using column chromatography (ethylacetate:hexane=1:4 to1:2) to afford the title compound. 0.07 g (5%).

mp: 144-147° C.

¹H-NMR (300 MHz, CDCl₃) δ 1.16 (d, J=6.9 Hz, 6H, CH₃) 1.25 (t, J=7.1 Hz,3H, CH₃) 2.78-2.85 (m, 1H, CH) 4.12-4.19 (q, J=14.3, 7.1 Hz, 2H, OCH₂)4.60 (s, 1H, OH) 6.69 (s, 1H, ArH) 6.88 (d, J=7.8 Hz, 1H, ArH) 7.47-7.58(m, 2H, ArH) 7.75-7.83 (m, 2H, ArH) 7.97 (d, J=7.6 Hz, 1H, ArH). MS(EI):368.

<Example 39> Methyl4b,9b-dihydroxy-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-8-carboxylate

Methyl 3-hydroxy-benzoate (0.42 g, 2.8 mmol) was added to a solution ofninhydrin (0.50 g, 2.8 mmol) in glacial acetic acid (10 ml) and heatedfor 27 hrs under reflux. The reaction mixture was diluted inethylacetate and washed many times with water, and the concentratedorganic layer was purified using column chromatography(ethylacetate:hexane=1:4) to afford the title compound. 0.14 g (16%).

mp: 220-223° C.

¹H-NMR (300 MHz, CDCl₃) δ 3.87 (s, 3H, OCH₃) 4.05 (s, 1H, OH) 4.79 (s,1H, OH) 6.87 (d, J=8.4 Hz, 1H, ArH) 7.59 (t, J=7.8 Hz, 1H, ArH)7.80-7.86 (m, 2H, ArH) 7.98-8.02 (m, 2H, ArH) 8.20 (s, 1H, ArH). MS(EI):312.

<Example 40>9b-Hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-4b-yldiethylcarbamate

Triethylamine (0.4 g, 4.0 mmol), diethylcarbamoyl chloride (0.91 g, 6.7mmol), and 4-dimethylaminopyridine (0.1 g) were added to a solution of4b,9b-dihydroxy-7-isopropyl-4b,9b-dihydro-5-oxa-indeno[2,1-a]inden-10-one(1.00 g, 3.3 mmol) in anhydrous tetrahydrofurane and heated underreflux. The reaction mixture was concentrated in a vacuum, diluted indichloromethane and washed many times with water. The concentratedorganic layer was purified using column chromatography(ethylacetate:hexane=1:4 to 1:2) to afford the title compound. 0.63 g(47%).

mp: 127-130° C.

¹H-NMR (300 MHz, CDCl₃) δ 1.08-1.29 (m, 12H, CH₃) 2.81-2.86 (m, 1H, CH)3.22-3.45 (m, 4H, NCH₂) 4.73 (s, 1H, OH) 6.70 (s, 1H, ArH) 6.91 (d,J=7.9 Hz, 1H, ArH) 7.53-7.61 (m, 2H, ArH) 7.78-7.91 (m, 3H, ArH).MS(EI): 395.

<Example 41>4b-Hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yldiethylcarbamate

Triethylamine (0.4 g, 4.0 mmol), diethylcarbamoyl chloride (0.91 g, 6.7mmol), and 4-dimethylaminopyridine (0.1 g) were added to a solution of4b,9b-dihydroxy-7-isopropyl-4b,9b-dihydro-5-oxa-indeno[2,1-a]inden-10-one(1.00 g, 3.3 mmol) in anhydrous tetrahydrofurane and heated underreflux. The reaction mixture was concentrated in a vacuum, diluted indichloromethane and washed many times with water. The concentratedorganic layer was purified using column chromatography(ethylacetate:hexane=1:4 to 1:2) to afford the title compound. 0.02 g(1.5%).

mp: 101-104° C.

¹H-NMR (300 MHz, CDCl₃) δ 1.06-1.30 (m, 12H, CH₃) 2.79-2.88 (m, 1H, CH)3.21-3.28 (m, 2H, NCH₂) 3.36-3.47 (m, 2H, NCH₂) 5.60 (s, 1H, OH) 6.73(s, 1H, ArH) 6.85 (d, J=7.2 Hz, 1H, ArH) 7.39 (d, J=7.8 Hz, 1H, ArH)7.54 (t, J=6.3 Hz, 1H, ArH) 7.78-7.88 (m, 2H, ArH) 8.00 (d, J=7.5 Hz,1H, ArH). MS(EI): 395.

<Example 42>2,3-Difluoro-4b,9b-dihydroxy-7-isopropyl-4bH-benzo[d]indeno[1,2-b]furan-10(9bH)-one

m-Isopropyl phenol (0.21 g, 1.5 mmol) was added to a solution of5,6-difluoro-2,2-dihydroxy-1H-indene-1,3(2H)-dione (0.33 g, 1.54 mmol)in glacial acetic acid (10 ml) and heated for 2 hrs under reflux. Thereaction mixture was diluted in ethylacetate and washed many times withwater. The concentrated organic layer was purified using columnchromatography (ethylacetate:hexane=1:4 to 1:2) to afford the titlecompound. 0.32 g (63%).

mp: 134-136° C.

¹H-NMR (300 MHz, CDCl₃) δ 1.18 (d, J=5.1 Hz, 6H, CH₃) 1.19 (s, 3H, CH₃)2.79-2.88 (m, 1H, CH) 3.71 (s, 1H, OH) 4.65 (s, 1H, OH) 6.72 (s, 1H,ArH) 6.87 (d, J=7.8 Hz, 1H, ArH) 7.37 (d, J=8.1 Hz, 1H, ArH) 7.56 (t,J=8.1 Hz, 1H, ArH) 7.77 (t, J=6.7 Hz, 1H, ArH). MS(EI): 332.

<Example 43>1,4b,9b-Trihydroxy-7-isopropyl-4bH-benzo[d]indeno[1,2-b]furan-10(9bH)-one

m-Isopropyl phenol (0.35 g, 2.5 mmol) was added to a solution of2,2,4-trihydroxy-1H-indene-1,3(2H)-dione (0.50 g, 2.5 mmol) in glacialacetic acid (10 ml) and heated for 4 hrs under reflux. The reactionmixture was diluted in ethylacetate and washed many times with water.The concentrated organic layer was purified using column chromatography(ethylacetate:hexane=1:2) to afford the title compound. 0.33 g (41%).

mp: 205-207° C.

¹H-NMR (300 MHz, CDCl₃) δ 1.19 (dd, J=1.8 Hz, 6.9 Hz, 6H, CH₃) 2.80-2.89(m, 1H, CH) 3.59 (s, 1H, OH) 4.60 (s, 1H, OH) 6.73 (s, 1H, ArH) 6.88(dd, J=1.5 Hz, 7.8 Hz, 1H, ArH) 6.95 (d, J=8.1 Hz, 1H, ArH) 7.45 (d,J=7.2 Hz, 2H, ArH) 7.69 (t, J=7.8 Hz, 1H, ArH) 8.40 (s, 1H, OH). MS(EI):312.

<Example 44> 4b,9b-Dihydroxy-7-isopropyl-1H-cyclopenta[b]naphthaleneo[1,2-b]furan-10(9bH)-one

m-Isopropyl phenol (0.03 g, 0.2 mmol) was added to a solution of2,2-dihydroxy-1H-cyclopenta[b]naphthalene-1,3(2H)-dione (50 mg, 0.2mmol) in glacial acetic acid (5 ml) and heated for 2 hrs under reflux.The reaction mixture was concentrated in a vacuum, and the concentratedorganic layer was purified using column chromatography(ethylacetate:hexane=1:4 to 1:3) to afford the title compound. 0.07 g(92%).

mp: 186-189° C.

¹H-NMR (300 MHz, CDCl₃) δ 1.09 (d, J=6.9 Hz, 6H, CH₃) 2.70-2.80 (m, 1H,CH) 6.67 (s, 1H, ArH) 6.76 (d, J=7.8 Hz, 1H, ArH) 7.41 (d, J=7.8 Hz, 1H,ArH) 7.48-7.61 (m, 2H, ArH) 7.92 (m, 2H, ArH) 8.26 (s, 1H, ArH) 8.43 (s,1H, ArH). MS(EI): 346.

<Example 45>9b-Hydroxy-7-isopropyl-4b-methoxy-1-nitro-4bH-benzo[d]indeno[1,2-b]furan-10(9bH)-one

Iron (0.09 g, 1.6 mmol), conc. HCl (0.05 ml), and water (0.5 ml) wereadded in that order to a solution of4b,9b-dihydroxy-7-isopropyl-1-nitro-4bH-benzo[d]indeno[1,2-b]furan-10(9bH)-one(80 mg, 0.2 mmol) in absolute ethanol (5 ml). The reaction mixture washeated for 2 hrs under reflux. After filtration at high temperature toremove iron, the filtrate was concentrated in a vacuum and purifiedusing column chromatography (ethylacetate:hexane=1:1) to afford thetitle compound. 80 mg (80%).

mp: 181-183° C.

¹H-NMR (300 MHz, CDCl₃) δ 1.19 (dd, J=2.7 Hz, 6.9 Hz, 6H, CH₃) 2.80-2.89(m, 1H, CH) 3.73 (s, 3H, OCH₃) 5.56 (s, 1H, OH) 6.59 (d, J=8.1 Hz, 1H,ArH) 6.73 (s, 1H, ArH) 6.86 (dd, J=1.5 Hz, 7.8 Hz, 1H, ArH) 7.08 (d,J=7.2 Hz, 1H, ArH) 7.46 (m, 2H, ArH). MS(EI): 326.

<Example 46>1-Amino-4b,9b-dihydroxy-7-isopropyl-4bH-benzo[d]indeno[1,2-b]furan-10(9bH)-one

Iron (0.48 g, 8.5 mmol), conc. HCl (0.1 ml), and water (1 ml) were addedin that order to a solution of4b,9b-dihydroxy-7-isopropyl-1-nitro-4bH-benzo[d]indeno[1,2-b]furan-10(9bH)-one(0.40 g, 1.1 mmol) in absolute ethanol (10 ml). The reaction mixture washeated for 2 hrs under reflux. After removing iron by high-temperaturefiltration, the remainder was concentrated in a vacuum and purified bycolumn chromatography (ethylacetate:hexane=1:4) to afford the titlecompound. 0.17 g (47%).

mp: 180-182° C.

¹H-NMR (300 MHz, CDCl₃) δ 1.19 (dd, J=1.8 Hz, 6.9 Hz, 6H, CH₃) 2.79-2.89(m, 1H, CH) 3.57 (s, 1H, OH) 4.57 (s, 1H, OH) 5.55 (s, 2H, NH₂) 6.61 (d,J=8.1 Hz, 1H, ArH) 6.77 (s, 1H, ArH) 6.85 (dd, J=1.5 Hz, 7.8 Hz, 1H,ArH) 7.17 (d, J=7.5 Hz, 1H, ArH) 7.42-7.52 (m, 2H, ArH). MS(EI): 311.

<Example 47>1-Amino-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furane-4b,9b-diyldiacetate

Iron (0.22 g, 3.8 mmol), conc. HCl (0.05 ml), and water (1 ml) wereadded in that order to a solution of7-isopropyl-1-nitro-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furane-4b,9b-diyldiacetate (0.23 g, 0.5 mmol) in absolute ethanol (10 ml). The reactionmixture was heated for 2 hrs under reflux. After removing iron byhigh-temperature filtration, the filtrate was concentrated in a vacuumand purified using column chromatography (ethylacetate:hexane=1:4) toafford the title compound. 0.15 g (71%).

mp: 220-223° C.

¹H-NMR (300 MHz, CDCl₃) δ 1.18 (dd, J=6.9 Hz, 2.1 Hz, 6H, CH₃) 2.15 (s,6H, OAc) 2.81-2.90 (m, 1H, CH) 5.57 (s, 2H, NH₂) 6.64 (d, J=8.1 Hz, 1H,ArH) 6.75 (s, 1H, ArH) 6.92 (dd, J=7.8 Hz, 1.2 Hz, 1H, ArH) 7.29 (d,J=7.8 Hz, 1H, ArH) 7.43-7.51 (m, 2H, ArH). ¹³C-NMR (300 MHz, CDCl₃) δ20.22, 21.40, 23.77, 23.82, 34.37, 87.36, 108.54, 110.02, 113.847,116.11, 117.79, 118.03, 121.31, 124.89, 137.49, 145.40, 147.37, 154.38,157.54, 167.18, 169.51, 194.17. MS(EI): 395.

<Example 48>N-(4b,9b-Dihydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-1-yl)acetamide

In absolute methanol (2 ml),1-acetamido-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furane-4b,9b-diyldiacetate (30 mg, 0.06 mmol) was reacted with potassium carbonate (0.05g, 0.3 mmol) at room temperature for 1 hr. The reaction mixture wasconcentrated in a vacuum, diluted in ethylacetate, and washed many timeswith water. The concentrated organic layer was purified using columnchromatography (ethylacetate:hexane=1:4 to 1:2) to afford the titlecompound. 7 mg (35%).

mp: 152-154° C.

¹H-NMR (300 MHz, CDCl₃) δ 1.18 (dd, J=1.9 Hz, 6.7 Hz, 6H, CH₃) 2.16 (s,3H, NHAc) 2.72-2.81 (m, 1H, CH) 3.76 (s, 1H, OH) 4.60 (s, 1H, OH) 6.65(s, 1H, ArH) 6.79 (d, J=8.1 Hz, 1H, ArH) 7.35 (d, J=7.8 Hz, 1H, ArH)7.53 (d, J=7.5 Hz, 1H, ArH) 7.66 (t, J=8.1 Hz, 1H, ArH) 8.44 (d, J=8.1Hz, 1H, ArH) 9.88 (s, 1H, NH). MS(EI): 353.

<Example 49> Methyl4b,9b-dihydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-1-ylcarbamate

A solution of4b,9b-dihydroxy-1-isocyanato-7-isopropyl-4bH-benzo[d]indeno[1,2-b]furan-10(9bH)-one(50 mg, 0.14 mmol) in absolute methanol (5 ml) was heated for 40 minunder reflux, concentrated in a vacuum, and purified using columnchromatography (ethylacetate:hexane=1:4) to afford the title compound.12 mg (22%).

mp: 96-99° C.

¹H-NMR (300 MHz, CDCl₃) δ 1.16 (dd, J=6.9, 1.8 Hz, 6H, CH₃) 2.77-2.87(m, 1H, CH) 3.80 (s, 3H, OCH₃) 6.70 (s, 1H, ArH) 6.84 (d, J=8.1 Hz, 1H,ArH) 7.41 (d, J=7.8 Hz, 1H, ArH) 7.54 (d, J=7.8 Hz, 1H, ArH) 7.71 (t,J=8.1 Hz, 1H, ArH) 8.23 (d, J=8.4 Hz, 1H, ArH) 9.37 (s, 1H, NH). MS(EI):369.

<Example 50>1-Amino-7-ethyl-4b,9b-dihydroxy-4b,9b-dihydro-5-oxa-indeno[2,1-a]inden-10-one

Iron (0.31 g, 5.57 mmol) and conc. HCl (0.05 ml) were added to asolution of7-ethyl-4b,9b-dihydroxy-1-nitro-4b,9b-dihydro-5-oxa-indeno[2,1-a]inden-10-one(0.25 g, 0.76 mmol) in ethanol (5 ml) and water (0.5 ml). After 2 hrs ofreaction, the reaction mixture was washed with methanol, and thefiltrate was concentrated and purified using column chromatography(ethylacetate:hexane=1:2) to afford the title compound. 0.05 g (22%).

mp: 200-203° C.

¹H-NMR (300 MHz, CDCl₃) δ 1.16 (t, J=7.5 Hz, 3H, CH₃) 2.57 (q, J=7.5 Hz,2H, CH₂) 5.47 (s, 2H, NH₂) 6.61 (d, J=8.1 Hz, 1H, ArH) 6.66 (s, 1H, ArH)6.80 (d, J=7.8 Hz, 1H, ArH) 7.14 (d, J=7.5 Hz, 1H, ArH) 7.29-7.39 (m,2H, ArH). MS(EI): 297.

<Example 51>7-Ethyl-4b,9b-dihydroxy-1-nitro-4b,9b-dihydro-5-oxa-indeno[2,1-a]inden-10-one

Triethylamine (0.09 g, 0.96 mmol) and chloroformic acid methyl ester(0.09 g, 0.96 mmol) were added to a solution of1-amino-4b,9b-dihydroxy-7-isopropyl-4b,9b-dihydro-5-oxa-indeno[2,1-a]inden-10-one(0.10 g, 0.32 mmol) in anhydrous tetrahydrofurane (15 ml), and heatedfor 14 hrs under reflux. The organic layer was concentrated and purifiedusing column chromatography (ethylacetate:hexane=1:4 to 1:2) to affordthe title compound. 80 mg (58%).

mp: 110-120° C.

¹H-NMR (300 MHz, CDCl₃) δ 1.19 (d, J=6.9 Hz, 6H, CH₃) 2.84-2.89 (m, 1H,CH) 3.71 (s, 3H, OCH₃) 3.76 (s, 3H, OCH₃) 5.67 (s, 2H, NH₂) 6.88-6.93(m, 2H, ArH) 7.19 (d, J=8.4 Hz, 1H, ArH) 7.25 (d, J=7.5 Hz, 1H, ArH)7.56 (t, J=7.8 Hz, 1H, ArH) 7.66 (d, J=8.4 Hz, 1H, ArH).

MS(EI): 427.

<Example 52>7-Ethyl-2,4b,9b-trihydroxy-4b,9b-dihydro-5-oxa-indeno[2,1-a]inden-10-one

m-Ethyl phenol (0.60 g, 4.97 mmol) was added to a solution of2,2,5-trihydroxy-2H-indene-1,3-dione (0.99 g, 4.97 mmol) in acetic acid(10 ml) and heated for 10 hrs under reflux. The filtrate wasconcentrated and subjected to column chromatography(ethylacetate:hexane=1:4) to afford the title compound. 1.02 g (69%).

mp: 208-213° C.

¹H-NMR (300 MHz, CDCl₃) δ 1.17 (t, J=7.5 Hz, 3H, CH₃) 2.57 (q, J=15.0Hz, 7.5 Hz, 2H, CH₂) 6.64 (s, 3H, ArH) 6.79 (d, J=7.8 Hz, 1H, ArH) 6.97(dd, J=8.5 Hz, 1.9 Hz 1H, ArH) 7.28 (s, 1H, ArH) 7.42 (d, J=7.8 Hz, 1H,ArH) 7.65 (d, J=8.5 Hz, 1H, ArH). MS(EI): 298.29.

<Example 53> Acetic acid4b-acetoxy-1-amino-7-isopropyl-10-oxo-4b,10-dihydro-5-oxa-indeno[2,1-a]inden-9b-ylester

Triethylamine (0.11 g, 1.16 mmol) was added to a solution of4b,9b-dihydroxy-7-isopropyl-1-nitro-4b,9b-dihydro-5-oxa-indeno[2,1-a]inden-10-one(0.20 g, 0.58 mmol) in anhydrous chloroform (10 ml) at room temperature.To this reaction mixture, a dilution of 10% acetyl chloride (1 ml) inchloroform was slowly added at 0° C. and incubated at the sametemperature for 1 hr. The reaction mixture was diluted indichloromethane and washed many times with water. The concentratedorganic layer was purified using column chromatography(ethylacetate:hexane=1:4 to 1:2) to afford the title compound. 30 mg(12%).

mp: 201-203° C.

¹H-NMR (300 MHz, CDCl₃) δ 1.21 (dd, J=8.4 Hz, 2.0 Hz, 6H, CH₃) 2.16 (s,6H, OAc) 2.85-2.90 (m, 1H, CH) 6.75 (s, 1H, ArH) 6.96 (d, J=7.9 Hz, 1H,ArH) 7.49 (d, J=7.9 Hz, 1H, ArH) 7.88-7.91 (m, 2H, ArH) 8.39 (dd, J=6.7Hz, 2.0 Hz, 1H, ArH). MS(EI): 425.

<Example 54> acetic acid4b-acetoxy-7-isopropyl-1-methanesulfonylamino-10-oxo-4b,10-dihydro-5-oxa-indeno[2,1-a]inden-9b-ylester

Triethylamine (0.05 g, 0.50 mmol) was added to a solution of acetic acid4b-acetoxy-1-amino-7-isopropyl-10-oxo-4b,10-dihydro-5-oxa-indeno[2,1-a]inden-9b-ylester (0.10 g, 0.25 mmol) in anhydrous chloroform (10 ml) at roomtemperature. To this solution, 0° C.

methanesulfonyl chloride (0.05 g, 0.50 mmol) was slowly added at 0° C.and reacted at room temperature for 12 hrs. The reaction mixture wasdiluted in dichloromethane and washed many times with water. The organiclayer was dried and filtered, followed by purification through columnchromatography (ethylacetate:hexane=1:2 to 1:1) to afford the titlecompound. 10 mg (8%).

mp: 96-100° C.

¹H-NMR (300 MHz, CDCl₃) δ 1.19 (d, J=6.9 Hz, 6H, CH₃) 2.07 (s, 3H, OAc)2.20 (s, 3H, OAc) 2.83-2.88 (m, 1H, CH) 3.16 (s, 3H, CH₃) 6.83 (s, 1H,ArH) 7.14 (d, J=8.1 Hz, 1H, ArH) 7.59 (q, J=8.1 Hz, 1H, ArH) 7.67 (d,J=7.5 Hz, 1H, ArH) 7.86 (t, J=7.5 Hz, 1H, ArH) 7.98 (d, J=8.1 Hz, 1H,ArH) 9.23 (s, 1H, NH). MS(EI): 473.

<Example 55>1-(4b,9b-Dihydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-1-yl-3-isopropylurea

Isopropylamine (0.012 ml was dropwise added to a solution of4b,9b-dihydroxy-1-isocyanato-7-isopropyl-4bH-benzo[d]indeno[1,2-b]furan-10(9bH)-one(40 mg, 0.11 mmol) in anhydrous tetrahydrofurane.

The reaction mixture was heated for 12 hrs under reflux, concentrated ina vacuum, and purified using column chromatography(ethylacetate:hexane=1:4) to afford the title compound. 10 mg (21%).

mp: 81-85° C.

¹H-NMR (300 MHz, CDCl₃) δ 0.98 (t, J=7.4 Hz, 6H, CH₃) 1.15-1.32 (m, 6H,CH₃) 2.81-2.85 (m, 1H, CH) 3.78 (s, 1H, OH) 4.14 (t, J=6.6 Hz, 2H, NH,CH) 4.67 (s, 1H, OH) 6.72 (s, 1H, ArH) 6.86 (d, J=7.8 Hz, 1H, ArH) 7.42(d, J=7.8 Hz, 1H, ArH) 7.53 (d, J=7.8 Hz, 1H, ArH) 7.71 (t, J=8.0 Hz,1H, ArH) 8.27 (d, J=8.3 Hz, 1H, ArH) 9.36 (s, 1H, NH). MS(EI): 396.

<Example 56>N-(9b-Amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-1-ylacetamide

To a solution ofN-(4b-chloro-9b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-1-ylacetamide(0.53 g, 1.4 mmol in anhydrous tetrahydrofurane (10 ml) was added 2Mammonia (1.42 ml in isopropylalcohol) at 5° C., and the reaction mixturewas stirred at room temperature for 2 hrs. After concentration in avacuum, the reaction mixture was diluted in dichloromethane, and washedwith an aqueous sodium bicarbonate solution. The concentrated organiclayer was purified using column chromatography (ethylacetate:hexane=1:4)to afford the title compound. 40 mg (8%).

mp: 152-156° C.

¹H-NMR (300 MHz, CDCl₃) δ 1.17 (dd, J=1.8, 6.9 Hz, 6H, CH₃) 2.23 (s, 3H,CH₃) 2.78-2.87 (m, 1H, CH) 6.70 (s, 1H, ArH) 6.84 (d, J=7.8 Hz, 1H, ArH)7.34 (d, J=7.8 Hz, 1H, ArH) 7.63 (d, J=7.2 Hz, 1H, ArH) 7.75 (t, J=8.1Hz, 1H, ArH) 8.54 (d, J=8.1 Hz, 1H, ArH) 9.99 (s, 1H, NH). MS(EI): 352.

<Example 57>N,N′-(4b-Hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furane-1,9b-diyl)diacetamide

N-(9b-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-1-yl)acetamide(400 mg, 0.11 mmol) was dissolved in anhydrous acetic acid (3 ml) wasreacted with anhydrous acetic acid (0.01 g, 0.11 mmol) for 2 hrs at 80°C. The reaction mixture was concentrated in a vacuum and purified usingcolumn chromatography (ethylacetate:hexane=1:4) to afford the titlecompound. 12 mg (27%).

mp: 189-191° C.

¹H-NMR (300 MHz, CDCl₃) δ 1.16 (dd, J=2.1, 6.9 Hz, 6H, CH₃) 2.03 (s, 3H,CH₃) 2.20 (s, 3H, CH₃) 2.77-2.86 (m, 1H, CH) 5.40 (s, 1H, OH) 6.52 (s,1H, NH) 6.70 (s, 1H, ArH) 6.84 (dd, J=1.2, 8.1 Hz, 1H, ArH) 7.29 (d,J=8.1 Hz, 1H, ArH) 7.57 (d, J=7.5 Hz, 1H, ArH) 7.72 (t, J=8.1 Hz, 1H,ArH) 8.54 (d, J=8.1 Hz, 1H, ArH) 10.00 (s, 1H, NH). MS(EI): 394.

<Example 58>N-(7-Amino-2-hydroxy-2-(4-isopropyl-2-hydroxyphenyl)-1,3-dioxo-2,3-dihydro-1H-inden-4-yl)acetamide

Water (1.5 ml), iron (0.71 g), and conc. HCl (0.05 ml) were added inthat order to a solution of1-amino-4b,9b-dihydroxy-7-isopropyl-4-nitro-4bH-benzo[d]indeno[1,2-b]furan-10(9bH)-one(0.70 g, 1.75 mmol) in ethanol (15 ml) and heated for 2 hrs underreflux. The reaction mixture was washed with methanol, concentrated in avacuum, and purified using column chromatography(ethylacetate:hexane=1:1) to afford the title compound. 0.33 g (51%).

mp: 278-280° C.

¹H-NMR (300 MHz, acetone-d₆) δ 1.18 (dd, J=6.3 Hz, 6H, CH₃) 2.17 (s, 3H,CH₃) 2.78-2.86 (m, 1H, CH) 6.38 (m, 2H, NH, ArH) 6.65 (s, 2H, ArH) 6.83(d, J=8.1 Hz, 2H, ArH). MS(EI): 368.

<Example 59>N-(2-Amino-4b,9b-dihydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-1-yl)acetamide

Water (0.3 ml), iron (0.10 g), and conc. HCl (0.05 ml) were added inthat order to a solution ofN-(4b,9b-dihydroxy-7-isopropyl-2-nitro-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-1-yl)acetamide(0.10 g, 0.25 mmol) in ethanol (3 ml) and heated for 90 min underreflux. The reaction mixture was washed with methanol, concentrated in avacuum and purified using column chromatography(ethylacetate:hexane=2:1) to afford the title compound. 22 mg (24%).

mp: 177-181° C.

¹H-NMR (300 MHz, acetone-d₆) δ 1.16 (d, J=3.0, 6.9 Hz, 6H, CH₃) 2.30 (s,3H, CH₃) 2.77-2.86 (m, 1H, CH) 5.93 (s, 2H, NH₂) 6.62 (s, 1H, ArH) 6.79(d, J=7.8 Hz, 1H, ArH) 6.99 (s, 1H, ArH) 7.29-7.40 (m, 2H, ArH) 8.86 (s,1H, NH).

<Example 60>1-Amino-4b,9b-dihydroxy-7-isopropyl-2-nitro-4bH-indeno[1,2-b]benzofuran-10(9bH)-one

N-(2,2-Dihydroxy-7-nitro-1,3-dioxo-2,3-dihydro-1H-inden-4-yl)acetamide(0.10 mg, 0.25 mmol) was dissolved in 6 M HCl (1.4 ml) and methanol (1ml) and heated for 90 min at 90° C. This solution was added with sodiumcarbonate and 2 N NaOH, and extracted with methylene chloride. Theorganic layer was concentrated to afford the title compound. 87 mg(97%).

mp: 12-116° C.

¹H-NMR (300 MHz, CDCl₃) δ 1.19 (d, J=6.9 Hz, 6H, CH₃) 2.83-2.88 (m, 1H,CH) 4.60 (s, 1H, OH) 6.75 (s, 1H, ArH) 6.90 (d, J=6.9 Hz, 1H, ArH) 7.19(d, J=8.4 Hz, 1H, ArH) 7.43 (d, J=8.1 Hz, 1H, ArH) 7.96 (s, 2H, NH₂)8.56 (d, J=9.0 Hz, 1H, ArH). MS(EI): 356.

<Example 61>1,4-diamino-4b,9b-dihydroxy-7-isopropyl-4bH-benzo[d]indeno[1,2-b]furan-10(9bH)-one

Water (1.5 ml), iron (0.68 g), and conc. HCl (0.05 ml) were added inthat order to a solution of1-amino-4b,9b-dihydroxy-7-isopropyl-4-nitro-4bH-benzo[d]indeno[1,2-b]furan-10(9bH)-one(0.60 g, 1.68 mmol) in ethanol (15 ml) and heated for 2 hrs underreflux. The reaction mixture was washed with methanol, concentrated in avacuum, and purified using column chromatography(ethylacetate:hexane=1:2) to afford the title compound. 0.22 g (36%).

mp: 223-231° C.

¹H-NMR (300 MHz, CD₃OD) δ 1.19 (d, J=6.9 Hz, 6H, CH₃) 2.78-2.82 (m, 1H,CH) 6.56 (s, 1H, ArH) 6.77 (d, J=8.1 Hz, 1H, ArH) 6.99 (s, 2H, ArH) 7.43(d, J=8.1 Hz, 1H, ArH). MS(EI): 326.

<Example 62>1,2-Diamino-4b,9b-dihydroxy-7-isopropyl-4bH-indeno[1,2-b]benzofuran-10(9bH)-one

Water (0.3 ml), iron (0.08 g), and conc. HCl (0.03 ml) were added inthat order to a solution of1-amino-4b,9b-dihydroxy-7-isopropyl-2-nitro-4bH-benzo[d]indeno[1,2-b]furan-10(9bH)-one(75 mg, 0.21 mmol) in ethanol (3 ml) and heated for 90 min under reflux.The reaction mixture was washed with methanol, concentrated in a vacuum,and purified using column chromatography (ethylacetate:hexane=1:1) toafford the title compound. 12 mg (17%).

mp: 163-166° C.

¹H-NMR (300 MHz, acetone-d₆) δ 1.03 (d, J=6.9 Hz, 6H, CH₃) 2.61-2.70 (m,1H, CH) 5.46 (s, 1H, ArH) 6.01 (s, 1H, ArH) 6.51-6.58 (m, 2H, ArH) 6.98(d, J=9.0 Hz, 1H, ArH). MS(EI): 326.

<Example 63>2-(2-Hydroxy-4-isopropylphenyl)-1,3-dioxo-2,3-dihydro-1H-inden-2-yldimethylcarbamate

Dimethyl carbamoyl chloride (0.72 g, 6.7 mmol) and trimethylamine (0.41g, 4.0 mmol) were added to a solution of 4-dimethylaminopyridine (0.1 g)4b,9b-dihydroxy-7-isopropyl-4b,9b-dihydro-5-oxa-indeno[2,1-a]inden-10-one(1.00 g, 3.3 mmol) in anhydrous tetrahydrofurane (10 ml) and heated for24 hrs under reflux. The reaction product was concentrated, andextracted with ethylacetate. The concentrated organic layer was purifiedusing column chromatography (ethylacetate:hexane=1:4 to 1:2) to affordthe title compound. 0.19 g (15%).

mp: 114-118° C.

¹H-NMR (300 MHz, CDCl₃) δ 1.19 (d, J=6.8 Hz, 6H, CH₃) 2.78-2.91 (m, 4H,CH, NCH₃) 3.06 (s, 3H, NCH₃) 5.57 (s, 1H, OH) 6.72 (s, 1H, ArH) 6.88 (d,J=7.8 Hz, 1H, ArH) 7.51 (d, J=8.1 Hz, 1H, ArH) 7.56-7.78 (m, 3H, ArH)7.99 (d, J=7.8 Hz, 1H, ArH). MS(EI): 367.

<Example 64>4b,9b-Dihydroxy-6,8-diisopropyl-4b,9b-dihydro-5-oxa-indeno[2,1-a]inden-10-one

To a solution of ninhydrin (0.30 g, 1.68 mmol) in acetic acid (10 ml)was added 2,4-diisopropylphenol (0.27 g, 1.51 mmol) which was thenheated for 12 hrs under reflux. After vacuum concentration,recrystallization in methylene chloride afforded the title compound(0.40 g, 70%).

mp: 205-206° C.,

¹H-NMR (300 MHz, CDCl₃) δ 1.14-1.24 (m, 12H), 2.81 (q, J=7.2 Hz, 1H),3.07 (q, J=7.2 Hz, 1H), 3.65 (s, 1H), 4.55 (s, 1H), 7.00 (d, J=1.7 Hz,1H), 7.17 (s, 1H), 7.54 (d, J=8.4 Hz, 1H), 7.76-7.81 (m, 2H), 8.00 (d,J=7.6 Hz, 1H).

<Example 65>9b-Amino-4b-hydroxy-7-isopropyl-4b,9b-dihydro-5-oxa-indeno[2,1-a]inden-10-one

Oxalyl chloride (0.69 ml, 8.15 mmol) and two drops of dimethylformamidewere added to a solution of4b,9b-dihydroxy-7-isopropyl-4b,9b-dihydro-5-oxa-indeno[2,1-a]inden-10-one(2.00 g, 6.79 mmol) in methylene chloride (20 ml) and stirred at roomtemperature for 3 hrs. Concentration in a vacuum gave9b-chloro-4b-hydroxy-7-isopropyl-4b,9b-dihydro-5-oxa-indeno-[2,1-a]inden-10-one(2.33 g, 109%).

9b-Chloro-4b-hydroxy-7-isopropyl-4b,9b-dihydro-5-oxa-indeno-[2,1-a]inden-10-one(1.00 g, 3.18 mmol) was dissolved in tetrahydrofurane (10 ml), cooled to5° C., and mixed with 2.0 M ammonia in isopropyl alcohol (3.18 ml, 6.36mmol) at room temperature for 4 hrs with stirring. After concentrationin a vacuum, purification through column chromatography (ethylacetate:hexane=1:4) afforded the title compound (0.75 g, 80%).

mp: 151-152° C.,

¹H-NMR (300 MHz, CDCl₃) δ 1.16 (dd, J=1.9 Hz, 7.0 Hz, 6H), 2.81 (q,J=7.2 Hz, 1H), 6.68 (s, 1H), 6.81 (d, J=7.8 Hz, 1H), 7.33 (d, J=7.8 Hz,1H), 7.51 (t, J=8.3 Hz, 1H), 7.73-7.80 (m, 2H), 8.01 (d, J=7.8 Hz, 1H).

<Example 66>N-(4b-Hydroxy-7-isopropyl-10-oxo-4b,10-dihydro-5-oxa-indeno[2,1-a]inden-9b-yl)-acetamide

Anhydrous acetic acid (0.08 ml, 0.88 mmol) was added to a solution of9b-amino-4b-hydroxy-7-isopropyl-4b,9b-dihydro-5-oxa-indeno[2,1-a]inden-10-one(0.26 g, 0.88 mmol) in acetic acid (5 ml) and heated for 2 hrs underreflux. Concentration in a vacuum and recrystallization in methylenechloride afforded the title compound (0.25 g, 84%).

mp: 183-184° C.,

¹H-NMR (300 MHz, CDCl₃) δ 1.15 (d, J=3.0 Hz, 3H), 1.17 (d, J=3.0 Hz,3H), 2.06 (s, 3H), 2.81 (q, J=7.1 Hz, 1H), 5.73 (s, 1H), 6.70 (d, J=1.1Hz, 1H), 6.81 (dd, J=1.4 Hz, 7.9 Hz, 1H), 7.25 (d, J=7.2 Hz, 1H), 7.54(t, J=8.2 Hz, 1H), 7.76-7.82 (m, 2H), 7.99 (d, J=7.7 Hz, 1H).

<Example 67>9b-Hexylamino-4b-hydroxy-7-isopropyl-4b,9b-dihydro-5-oxa-indeno[2,1-a]inden-10-one

To a solution of4b,9b-dihydroxy-7-isopropyl-4b,9b-dihydro-5-oxa-indeno[2,1-a]inden-10-one(1.00 g, 3.39 mmol) in methylene chloride (10 ml) were added oxalylchloride (0.35 ml, 4.08 mmol) and two drops of dimethylformamide,followed by stirring at room temperature for 3 hrs. concentration in avacuum gave9b-chloro-4b-hydroxy-7-isopropyl-4b,9b-dihydro-5-oxa-indeno-[2,1-a]inden-10-one(1.33 g, 109%).

9b-chloro-4b-hydroxy-7-isopropyl-4b,9b-dihydro-5-oxa-indeno[2,1-a]inden-10-one(1.00 g, 3.18 mmol) was dissolved in tetrahydrofurane (10 ml), cooled to5° C., and reacted with hexylamine (0.84 ml, 6.36 mmol) at roomtemperature for 3 hrs while stirring. Concentration in a vacuum andpurification through column chromatography (ethyl acetate:hexane=1:4)afforded the title compound (0.58 g, 48%).

¹H-NMR (300 MHz, CDCl₃) δ 0.84 (t, J=7.8 Hz, 3H), 1.15 (d, J=2.5 Hz,3H), 1.17 (d, J=2.7 Hz, 3H), 1.20-1.33 (m, 6H), 1.42-1.52 (m, 2H), 2.45(t, J=8.3 Hz, 2H), 2.81 (q, J=7.7 Hz, 1H), 6.69 (s, 1H), 6.81 (dd, J=1.0Hz, 7.9 Hz, 1H), 7.30 (d, J=7.6 Hz, 1H), 7.49 (t, J=8.6 Hz, 1H),7.73-7.78 (m, 2H), 8.00 (d, J=7.6 Hz, 1H).

<Example 68>9b-Amino-4b-hydroxy-6,8-diisopropyl-4b,9b-dihydro-5-oxa-indeno[2,1-a]inden-10-one

To a solution4b,9b-dihydroxy-6,8-diisopropyl-4b,9b-dihydro-5-oxa-indeno[2,1-a]inden-10-one(0.30 g, 0.88 mmol) in methylene chloride (10 ml) were oxalyl chloride(0.35 ml, 4.08 mmol) and two drops of dimethylformamide, followed byreaction at room temperature for 3 hrs while stirring. Concentration ina vacuum gave9b-chloro-4b-hydroxy-6,8-diisopropyl-4b,9b-dihydro-5-oxa-indeno[2,1-a]inden-10-one(0.35 g, 111%).

9b-chloro-4b-hydroxy-6,8-diisopropyl-4b,9b-dihydro-5-oxa-indeno[2,1-a]inden-10-one(0.35 g, 0.98 mmol) was dissolved in tetrahydrofurane (10 ml), cooled to5° C., and reacted with, 2.0 M ammonia in isopropyl alcohol (0.98 ml,1.96 mmol) at room temperature for 4 hrs. Concentration in a vacuum andpurification through column chromatography (ethyl acetate:hexane=1:2)afforded the title compound (0.10 g, 30%).

mp: 199-200° C.

¹H-NMR (300 MHz, CDCl₃) δ 1.15-1.23 (m, 12H), 2.80 (q, J=7.3 Hz, 1H),3.06 (q, J=7.3 Hz, 1H), 4.43 (s, 2H), 7.00 (d, J=1.4 Hz, 1H), 7.21 (d,J=1.6 Hz, 1H), 7.51 (t, J=9.0 Hz, 1H), 7.73-7.80 (m, 2H), 8.00 (d, J=6.8Hz, 1H).

<Example 69>4b-Hydroxy-9b-isocyanato-7-isopropyl-4b,9b-dihydro-5-oxa-indeno[2,1-a]-inden-10-one

To a solution of9b-amino-4b-hydroxy-7-isopropyl-4b,9b-dihydro-5-oxa-indeno[2,1-a]inden-10-one(0.50 g, 1.69 mmol) in toluene (10 ml) were added triethylamine (0.26ml, 1.86 mmol) and triphosgene (0.55 g, 1.86 mmol), followed by heatingfor 3 hrs under reflux. After vacuum concentration, the concentrate waspurified using column chromatography (ethyl acetate:hexane=1:2) toafford the title compound (0.40 g, 73%).

mp: 150-152° C.

¹H-NMR (300 MHz, CDCl₃) δ 1.16 (d, J=3.1 Hz, 3H), 1.18 (d, J=3.1 Hz,3H), 2.85 (q, J=7.4 Hz, 1H), 6.82 (s, 1H), 6.90 (dd, J=1.0 Hz, 7.9 Hz,1H), 7.51 (d, J=8.0 Hz, 1H), 7.65 (t, J=8.6 Hz, 1H), 7.77 (s, 1H),7.85-7.89 (m, 2H), 8.01 (d, J=8.0 Hz, 1H).

<Example 70>(9b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-5-oxa-indeno[2,1-a]inden-4b-yl)-carbamicacid methyl ester

To a solution of9b-amino-4b-hydroxy-7-isopropyl-4b,9b-dihydro-5-oxa-indeno[2,1-a]inden-10-one(0.30 g, 1.01 mmol) in tetrahydrofurane (10 ml) were added triethylamine(0.17 ml, 1.21 mmol) and methyl chloroformate (0.07 ml, 1.01 mmol),followed by reaction at room temperature for 3 hrs while stirring.

After vacuum concentration, the concentrate was extracted with water andmethylene chloride, and purified using column chromatography (ethylacetate:hexane=1:2) to afford the title compound (30 mg, 8%).

mp: 150-152° C.

¹H-NMR (300 MHz, CDCl₃) δ 1.15 (d, J=3.0 Hz, 3H), 1.17 (d, J=3.1 Hz,3H), 2.82 (q, J=7.8 Hz, 1H), 3.66 (s, 3H), 5.54 (s, 1H), 5.94 (s, 1H),6.70 (s, 1H), 6.83 (d, J=7.5 Hz, 1H), 7.28 (d, J=7.9 Hz, 1H), 7.55 (t,J=8.7 Hz, 1H), 7.78-7.84 (m, 2H), 8.01 (d, J=7.9 Hz, 1H).

<Example 71> Pentanoic acid(9b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-5-oxa-indeno[2,1-a]inden-4b-yl)-amide

To a solution of9b-amino-4b-hydroxy-7-isopropyl-4b,9b-dihydro-5-oxa-indeno[2,1-a]inden-10-one(0.30 g, 1.01 mmol) in tetrahydrofurane (10 ml) were added triethylamine(0.17 ml, 1.21 mmol) and valeroyl chloride (0.12 ml, 1.01 mmol),followed by reaction at room temperature for 1 hr while stirring.

After vacuum concentration, the concentrate was extracted with water andmethylene chloride, and purified by column chromatography (ethylacetate:hexane=1:4) to afford the title compound (0.21 g, 55%).

mp: 110-112° C.

¹H-NMR (300 MHz, CDCl₃) δ 0.89 (t, J=8.0 Hz, 3H), 1.15 (d, J=3.3 Hz,3H), 1.17 (d, J=3.1 Hz, 3H), 1.28-1.38 (m, 2H), 1.54-1.64 (m, 2H), 2.30(t, J=9.1 Hz, 2H), 2.82 (q, J=7.8 Hz, 1H), 5.73 (s, 1H), 6.63 (s, 1H),6.71 (d, J=1.3 Hz, 1H), 6.81 (dd, J=1.1 Hz, 7.9 Hz, 1H), 7.24 (d, J=7.5Hz, 1H), 7.55 (t, J=8.0 Hz, 1H), 7.77-7.84 (m, 2H), 8.01 (d, J=7.7 Hz,1H).

<Example 72>N-(9b-Hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-5-oxa-indeno[2,1-a]inden-4b-yl)-isobutylamide

To a solution of9b-amino-4b-hydroxy-7-isopropyl-4b,9b-dihydro-5-oxa-indeno[2,1-a]inden-10-one(0.30 g, 1.01 mmol) in tetrahydrofurane (10 ml) were added triethylamine(0.17 ml, 1.21 mmol) and isobutyryl chloride (0.10 ml, 1.01 mmol),followed by reaction at room temperature for 1 hr while stirring.

After vacuum concentration, the concentrate was extracted with water andmethylene chloride, and purified by column chromatography (ethylacetate:hexane=1:2) to afford the title compound (0.21 g, 54%).

mp: 109-111° C.

¹H-NMR (300 MHz, CDCl₃) δ 1.17 (d, J=6.7 Hz, 12H), 2.51 (q, J=7.2 Hz,1H), 2.82 (q, J=7.7 Hz, 1H), 5.73 (s, 1H), 6.63 (s, 1H), 6.71 (s, 1H),6.81 (d, J=7.7 Hz, 1H), 7.24 (d, J=8.3 Hz, 1H), 7.55 (t, J=8.1 Hz, 1H),7.76-7.86 (m, 2H), 8.00 (d, J=7.6 Hz, 1H).

<Example 73>N-(1-Amino-9b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-5-oxa-indeno[2,1-a]inden-4b-yl)-acetamide

To a solution ofN-(9b-hydroxy-7-isopropyl-1-nitro-10-oxo-9b,10-dihydro-5-oxa-indeno[2,1-a]inden-4b-yl)-acetamide(0.30 g, 0.78 mmol) in ethanol/water (9 ml/0.9 ml) were added iron (0.30g, 5.46 mmol) and one drop of conc. HCl, followed by heating for 1 hrunder reflux. After neutralization with sodium bicarbonate, the reactionmixture was concentrated in a vacuum and purified by columnchromatography (ethyl acetate:hexane=1:1) to afford the title compound(0.20 g, 72%).

mp: 278-280° C.

¹H-NMR (300 MHz, CD₃OD) δ 1.15 (d, J=7.0 Hz, 6H), 2.00 (s, 3H), 2.80 (q,J=7.0 Hz, 1H), 6.61-6.68 (m, 2H), 6.83 (d, J=7.5 Hz, 1H), 6.97 (d, J=7.2Hz, 1H), 7.35 (d, J=7.8 Hz, 1H), 7.41 (t, J=9.6 Hz, 1H).

<Example 74>N-(9b-Hydroxy-6,8-diisopropyl-10-oxo-9b,10-dihydro-5-oxa-indeno[2,1-a]inden-4b-yl)-acetamide

Anhydrous acetic acid (0.02 ml, 0.20 mmol) was added to a solution of9b-amino-4b-hydroxy-6,8-diisopropyl-4b,9b-dihydro-5-oxa-indeno[2,1-a]inden-10-one(70 mg, 0.20 mmol) in acetic acid (5 ml), and heated for 2 hrs underreflux. After neutralization with sodium bicarbonate, the reactionmixture was concentrated in a vacuum and purified by columnchromatography (ethyl acetate:hexane=1:1) to afford the title compound(50 mg, 66%).

mp: 217-219° C.

¹H-NMR (300 MHz, CDCl₃) δ 1.15 (d, J=7.0 Hz, 3H), 1.19 (d, J=3.6 Hz,3H), 1.21 (d, J=2.4 Hz, 3H), 1.23 (d, J=5.7 Hz, 3H), 2.20 (s, 3H), 2.85(q, J=6.7 Hz, 1H), 3.06 (q, J=7.6 Hz, 1H), 7.05 (d, J=1.7 Hz, 1H), 7.25(d, J=1.7 Hz, 1H), 7.56 (t, J=8.3 Hz, 1H), 7.74-7.82 (m, 2H), 7.96 (d,J=7.6 Hz, 1H).

<Example 75>N-(9b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-5-oxa-indeno[2,1-a]inden-4b-yl)-N-methyl-acetamide

Anhydrous acetic acid (0.03 ml, 0.32 mmol) was added to a solution of4b-hydroxy-7-isopropyl-9b-methylamino-4b,9b-dihydro-5-oxa-indeno[2,1-a]inden-10-one(0.10 g, 0.32 mmol) in acetic acid (5 ml), and heated for 2 hrs underreflux. After neutralization with sodium bicarbonate, the reactionmixture was concentrated in a vacuum and purified by columnchromatography (ethyl acetate:hexane=1:1) to afford the title compound(70 mg, 62%).

mp: 216-217° C.

¹H-NMR (300 MHz, CD₃OD) δ 1.17 (d, J=6.7 Hz, 6H), 2.13 (s, 3H),2.75-2.90 (m, 3H), 6.69 (s, 1H), 6.84 (d, J=7.6 Hz, 1H), 7.34 (d, J=8.0Hz, 1H), 7.44 (t, J=8.4 Hz, 1H), 7.64 (t, J=8.3 Hz, 1H), 7.71 (d, J=7.6Hz, 1H), 7.80 (d, J=7.6 Hz, 1H).

<Example 76>1-(4b-Hydroxy-7-isopropyl-1-nitro-10-oxo-4b,10-dihydro-5-oxa-indeno[2,1-a]inden-9b-yl)-3-isopropyl-urea

Triphosgene (0.28 g, 0.97 mmol) was added to a solution of9b-amino-4b-hydroxy-7-isopropyl-1-nitro-4b,9b-dihydro-5-oxa-indeno[2,1-a]inden-10-one(0.30 g, 0.88 mmol) in tetrahydrofurane (10 ml) and stirred at roomtemperature for 2 hrs. Concentration in a vacuum and purificationthrough column chromatography (ethyl acetate:hexane=1:2) gave4b-hydroxy-9b-isocyanato-7-isopropyl-1-nitro-4b,9b-dihydro-5-oxa-indeno[2,1-a]inden-10-one(0.20 g, 62%).

4b-hydroxy-9b-isocyanato-7-isopropyl-1-nitro-4b,9b-dihydro-5-oxa-indeno[2,1-a]inden-10-one(0.20 g, 0.54 mmol) was dissolved in tetrahydrofurane (10 ml), addedwith triethylamine (0.18 ml, 1.30 mmol) and isopropyl amine (0.05 ml,0.65 mmol), and heated for 48 hrs under reflux.

After vacuum concentration, the concentrate was extracted with water andmethylene chloride, and purified by column chromatography (ethylacetate:hexane=1:1) to afford the title compound (40 mg, 17%).

mp: 228-229° C.

¹H-NMR (300 MHz, (CD₃)₂CO-d₆) δ 1.00 (d, J=6.8 Hz, 3H) 1.14 (d, J=4.5Hz, 3H), 1.17 (d, J=4.5 Hz, 3H), 1.50 (d, J=6.6 Hz, 3H), 2.78-2.88 (m,1H), 3.87 (q, J=7.2 Hz, 1H), 5.84 (s, 1H), 6.34 (s, 1H), 6.61 (s, 1H),6.66 (s, 1H), 6.84 (d, J=7.9 Hz, 1H), 7.46 (d, J=7.9 Hz, 1H), 7.77 (t,J=8.5 Hz, 1H), 8.08 (d, J=7.2 Hz, 1H), 8.19 (d, J=7.9 Hz, 1H).

<Example 77>N-(1-Amino-4b-hydroxy-7-isopropyl-10-oxo-4b,10-dihydro-5-oxa-indeno[2,1-a]inden-9b-yl)-isobutylamide

Iron (0.09 g, 1.70 mmol) and one drop of conc. HCl were added to asolution ofN-(4b-hydroxy-7-isopropyl-1-nitro-10-oxo-4b,10-dihydro-5-oxa-indeno[2,1-a]inden-9b-yl)-isobutylamide(100 mg, 0.24 mmol) in ethanol/water (3 ml/0.3 ml) and heated for 1 hrunder reflux. After neutralization with sodium bicarbonate, the reactionmixture was concentrated in a vacuum and purified by columnchromatography (ethyl acetate:hexane=1:1) to afford the title compound(60 mg, 66%).

mp: 141-143° C.

¹H-NMR (300 MHz, CDCl₃) δ 1.17 (d, J=6.7 Hz, 12H), 2.51 (q, J=7.2 Hz,1H), 2.83 (q, J=7.7 Hz, 1H), 5.60 (s, 2H), 6.67-6.72 (m, 1H), 6.78-6.82(m, 1H), 6.86-6.91 (m, 1H), 7.16 (t, J=7.7 Hz, 1H), 7.22 (d, J=6.7 Hz,1H), 7.46 (t, J=8.8 Hz, 1H).

<Example 78> Pentanoic acid(1-amino-4b-hydroxy-7-isopropyl-10-oxo-4b,10-dihydro-5-oxa-indeno[2,1-a]inden-9b-yl)-amide

To a solution of pentanoic acid(4b-hydroxy-7-isopropyl-1-nitro-10-oxo-4b,10-dihydro-5-oxa-indeno[2,1-a]inden-9b-yl)-amide(100 mg, 0.23 mmol) in ethanol/water (3 ml:0.3 ml) was added iron (0.09g, 1.64 mmol). After addition of one drop of conc. HCl, the solution wasrefluxed for 1 hr. After neutralization with sodium bicarbonate, thereaction mixture was concentrated in a vacuum and purified by columnchromatography (ethyl acetate:hexane=1:1) to afford the title compound(70 mg, 77%).

mp: 165-168° C.

¹H-NMR (300 MHz, CD₃OD) δ 0.93 (t, J=8.1 Hz, 3H), 1.17 (d, J=1.0 Hz,3H), 1.20 (d, J=1.0 Hz, 3H), 1.35-1.44 (m, 2H), 1.52-1.63 (m, 2H), 2.28(t, J=8.6 Hz, 2H), 2.84 (q, J=7.1 Hz, 1H), 6.65-6.72 (m, 2H), 6.86 (dd,J=1.1 Hz, 7.9 Hz, 1H), 6.99 (d, J=7.4 Hz, 1H), 7.37 (d, J=7.7 Hz, 1H),7.43 (t, J=8.6 Hz, 1H).

<Example 79>9b-Hydroxy-4b-(2-hydroxyethoxy)-7-isopropyl-4bH-benzo[d]indeno[1,2-b]furan-10(9bH)-one

Iodine (1.71 g, 6.74 mmol) was added to a solution of4b,9b-dihydroxy-7-isopropyl-4bH-benzo[d]indeno[1,2-b]furan-10(9bH)-one(1 g, 3.37 mmol) in ethylene glycol (20 ml) and stirred at roomtemperature for 3 hrs. After water (100 ml) was poured thereto, thesolution was extracted with ethyl acetate, and the reaction mixture waspurified by silica gel column chromatography (40% ethyl acetate inhexane) to afford the title compound. 0.40 g (39%).

mp: 100-105° C.

¹H-NMR (300 MHz, CDCl₃) δ 1.12-1.25 (m, 6H, CH₃) 2.51 (s, 1H, OH, D₂Oexchan gable) 2.82-2.86 (septet, 1H, CH), 3.83 (t, 2H, CH₂) 4.04-4.15(m, 3H, CH₂ and OH, D₂O exchan gable) 6.72 (s, 1H, ArH) 6.87 (d, J=7.8Hz, 1H, ArH) 7.42 (d, J=7.8 Hz, 1H, ArH) 7.57 (t, J=7.5 Hz, 1H, ArH)7.92 (t, J=7.5 Hz, 2H, ArH) 7.94 (d, J=7.8 Hz, 2H, ArH). MS(EI): 340.

<Example 80>4b,9b-Dihydroxy-7-isopropyl-1-nitro-4bH-benzo[d]indeno[1,2-b]furan-10(9bH)-one

A solution of 4-nitro-2,3-dihydro-1H-inden-1-one (1.50 g, 8.4 mmol) in1,4-dioxane (15 ml) and glacial acetic acid (3.5 ml) was added withcesium dioxide (1.87 g, 16.9 mmol), and refluxed at 110° C. for 2 hrs.After filtration, the filtrate was concentrated, mixed with water, andextracted with ethyl acetate. The reaction mixture was concentration togive 2,2-dihydroxy-4-nitro-2H-indene-1,3-dione (600 mg).

In glacial acetic acid (5 ml), 2,2-dihydroxy-4-nitro-2H-indene-1,3-dione(0.50 g, 2.24 mmol) and 3-isopropyl phenol (0.37 ml, 2.7 mmol) wererefluxed for 2 hrs. The reaction mixture was concentrated and purifiedby silica gel column chromatography (20% ethyl acetate in hexane) toafford the title compound as a white solid. 0.30 g (39%).

mp: 186-188° C.

¹H-NMR (300 MHz, CDCl₃) δ 1.15-1.18 (m, 6H, CH₃) 2.81-2.86 (septet, 1H,CH) 3.53 (s, 1H, OH) 6.24 (s, 1H, OH) 6.71 (s, 1H, ArH) 6.92 (d, J=7.9Hz, 1H, ArH) 7.48 (d, J=7.9 Hz, 1H, ArH) 7.79 (t, J=8.6 Hz, 1H, ArH)8.19 (d, J=7.7 Hz, 1H, ArH) 8.50 (d, J=7.1 Hz, 1H, ArH). MS(EI): 341.

<Example 81>4b,9b-Dihydroxy-7-isopropyl-2,3-dimethoxy-4bH-benzo[d]indeno[1,2-b]furan-10(9bH)-one

To a solution of 5,6-dimethoxy-2,3-dihydro-1H-inden-1-one (1.00 g, 5.2mmol) in 1,4 dioxane (20 ml) and glacial acetic acid (2 ml) was addedcesium dioxide (1.16 g, 10.4 mmol), followed by reaction at 110° C. for2 hrs while stirring. The reaction mixture was concentrated, diluted inwater, and extracted with ethyl acetate to give 0.80 g of2,2-dihydroxy-5,6-dimethoxy-2H-indene-1,3-dione.

In glacial acetic acid (6 ml),2,2-dihydroxy-5,6-dimethoxy-2H-indene-1,3-dione (0.55 g, 2.30 mmol) and3-isopropyl phenol (1.10 ml, 2.76 mmol) were refluxed for 2 hrs. Theconcentrated reaction mixture was purified by silica gel columnchromatography (30% ethyl acetate in hexane) to afford the titlecompound, white 0.22 g (57%).

mp: 127-129° C.

¹H-NMR (300 MHz, CDCl₃) δ 1.18 (d, J=6.9 Hz, 6H, CH₃) 2.81-2.86 (septet,1H, CH) 3.71 (s, 1H, OH) 3.9 (s, 3H, CH₃) 4.1 (s, 3H, CH₃) 4.6 (s, 1H,OH) 6.72 (s, 1H, ArH) 6.86 (d, J=7.8 Hz, 1H, ArH) 7.14 (s, 1H, ArH)7.37-7.43 (m, 2H, ArH). MS(EI): 356.

<Example 82>4b,9b-dihydroxy-7-isopropyl-2,3-dimethyl-4bH-benzo[d]indeno[1,2-b]furan-10(9bH)-one

To a solution of 5,6-dimethyl-2,3-dihydro-1H-inden-1-one (0.50 g, 3.12mmol) in 1,4-dioxane (10 ml) and glacial acetic acid (1 ml) was addedcesium dioxide (0.69 g, 6.24 mmol), followed by reaction at 110° C. for2 hrs while stirring. The reaction mixture was filtered through acellite layer, and the resulting organic solution was concentrated andpurified by silica gel column chromatography (40% ethyl acetate inhexane) to give 2,2-dihydroxy-5,6-dimethyl-2H-indene-1,3-dione. 0.40 g(63%).

2,2-dihydroxy-5,6-dimethyl-2H-indene-1,3-dione (0.35 g, 1.7 mmol) and3-isopropyl phenol (0.28 ml, 2.03 mmol) were dissolved in glacial aceticacid (4 ml) and refluxed for 4 hrs. The concentrated reaction mixturewas purified by silica gel column chromatography (30% ethyl acetate inhexane) to afford the title compound. White 0.39 g (71%).

mp: 138-140° C.

¹H-NMR (300 MHz, CDCl₃) δ 1.16 (d, J=6.9 Hz, 6H, CH₃) 2.30 (s, 3H, CH₃)2.40 (s, 3H, CH₃) 2.77-2.86 (septet, 1H, CH) 3.99 (s, 1H, OH) 4.73 (s,1H, OH) 6.70 (s, 1H, ArH) 6.81 (d, J=7.9 Hz, 1H, ArH) 7.39 (d, J=7.9 Hz,1H, ArH) 7.53 (s, 1H, ArH) 7.8 (s, 1H, ArH). MS(EI): 324.

<Example 83> Mixture of 6:4(4bS,9bS)-2-bromo-4b,9b-dihydroxy-7-isopropyl-4bH-benzo[d]indeno[1,2-b]furan-10(9bH)-oneand(4bS,9bS)-3-bromo-4b,9b-dihydroxy-7-isopropyl-4bH-benzo[d]indeno[1,2-b]furan-10(9bH)-one

To a solution of 5-bromo-2,3-dihydro-1H-inden-1-one (0.81 g, 3.83 mmol)in 1,4-dioxane (15 ml) and glacial acetic acid (1.5 ml) was added cesiumdioxide (0.94 g, 8.44 mmol), followed by reaction at 110° C. for 2.5 hrswhile stirring. The reaction mixture was filtered through a cellite pad,and the filtrate was concentrated and purified by silica gel columnchromatography (ethyl acetate:hexane=1:1) to give5-bromo-2,2-dihydroxy-2H-indene-1,3-dione 0.80 g.

5-bromo-2,2-dihydroxy-2H-indene-1,3-dione (0.70 g, 2.7 mmol) and3-isopropyl phenol (0.45 ml, 3.3 mmol) were dissolved in glacial aceticacid (8 ml) and refluxed for 4 hrs. The concentrated reaction mixturewas purified by silica gel column chromatography (ethylacetate:hexane=1:2) to afford the title compounds as a 6:4 mixture.White 760 mg (75%).

mp: 160-162° C.

¹H-NMR (300 MHz, CDCl₃) δ 1.12 (m, 6H, CH₃) 2.72-2.81 (septet, 1H, CH)5.12 (s, 1H, OH) 5.60 (s, 1H, OH) 6.63 (d, J=5.7 Hz, 1H, ArH) 6.75 (d,J=7.8 Hz, 1H, ArH) 7.32 (d, J=7.8 Hz, 1H, ArH) 7.49-7.59 (m, 1.3H, ArH)7.76-7.81 (m, 1H, ArH) 8.11 (s, 0.6H, ArH). MS(EI): 341.

<Example 84> Methyl(4bS,9bS)-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-ylcarbamate

A solution of2,3-dihydro-2-(4-isopropyl-2-methoxyphenyl)-1,3-dioxo-1H-inden-2-ylcarbamate(120 mg, 0.32 mmol) in dichloromethane (5 ml) was added at −78° C. over5 min to a solution of boron tribromide (1.0 M, 0.71 ml, 0.71 mmol) indichloromethane (3 ml), and stirred at −10° C. for 3 hrs. The reactionmixture was poured with water, extracted with dichloromethane, andpurified by silica gel column chromatography (30% ethyl acetate inhexane) to afford the title compound. 90 mg (78%).

mp: 161-163° C.

¹H-NMR (300 MHz, CDCl₃) δ 1.15-1.18 (m, 6H, CH₃) 2.82 (septet, J=6.9 Hz,1H, CH) 3.64 (s, 3H, OCH₃) 5.49 (s, 1H, OH) 5.93 (s, 1H, NH) 6.70 (s,1H, ArH) 6.82-6.85 (m, 1H, ArH) 7.25-7.29 (m, 1H, ArH) 7.53-7.59 (m, 1H,ArH) 7.79-7.84 (m, 2H, ArH) 8.00-8.03 (m, 1H, ArH). MS(EI): 353.

<Example 85> Isopropyl(4bS,9bS)-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-ylcarbamate

Boron tribromide (1.0 M in dichloromethane, 0.55 ml, 0.55 mmol) wasdissolved in dichloromethane (3 ml) and cooled to −78° C. To thissolution, isopropyl2-(4-isopropyl-2-methoxyphenyl)-1,3-dioxo-2,3-dihydro-1H-inden-2-ylcarbamate(100 mg, 0.25 mmol) in dichloromethane (5 ml) was dropwise added over 5min, and stirred at 0° C. for 4 hrs. The reaction mixture was pouredwith water, extracted with dichloromethane, and purified by silica gelcolumn chromatography (30% ethyl acetate in hexane) to afford the titlecompound. 45 mg (47%).

mp: 114-116° C.

¹H-NMR (300 MHz, CDCl₃) δ 1.15-1.18 (m, 12H, CH₃) 2.82 (septet, J=6.9Hz, 1H, CH) 4.83 (septet, J=6.3 Hz, 1H, CH) 5.83 (s, 1H, NH) 6.69 (d,J=1.5 Hz, 1H, ArH) 6.83 (dd, J=1.5 Hz, J=7.8 Hz, 1H, ArH) 7.29 (d, J=7.8Hz, 1H, ArH) 7.52-7.58 (m, 1H, ArH) 7.78-7.84 (m, 2H, ArH) 8.01 (d,J=7.5 Hz, 1H, ArH). MS(EI): 395.

<Example 86>ethyl(4bS,9bS)-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-ylcarbamate

Boron tribromide (1.0 M in dichloromethane, 4.3 ml, 4.3 mmol) wasdissolved in dichloromethane (15 ml), and cooled to −78° C. To thissolution, ethyl2-(4-isopropyl-2-methoxyphenyl)-1,3-dioxo-2,3-dihydro-1H-inden-2-ylcarbamate(750 mg, 1.96 mmol) in dichloromethane (20 ml) was dropwise added over10 min, and stirred at 0° C. for 4 hrs. The reaction mixture was pouredwith water, extracted with dichloromethane, and purified by silica gelcolumn chromatography (30% ethyl acetate in hexane) to afford the titlecompound. 500 mg (70%).

mp: 115-118° C.

¹H-NMR (300 MHz, CDCl₃) δ 1.14-1.17 (m, 9H, CH₃) 2.81 (septet, J=6.9 Hz,1H, CH) 4.03-4.09 (m, 2H, OCH₂) 5.67 (br, 1H, OH) 5.92 (br, 1H, NH) 6.68(s, 1H, ArH) 6.83 (dd, J=1.5 Hz, J=8.1 Hz, 1H, ArH) 7.29 (d, J=8.1 Hz,1H, ArH) 7.51-7.56 (m, 1H, ArH) 7.76-7.81 (m, 2H, ArH) 8.00 (d, J=7.5Hz, 1H, ArH). MS(EI): 367.

<Example 87>N,N′-((4bS,9bS)-4b-Hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furane-1,9b-diyl)diacetamide

Boron tribromide (1.0 M in dichloromethane, 1.32 ml, 1.32 mmol) wasdissolved in dichloromethane (5 ml) and cooled to −78° C. To thissolution,N,N′-(2-(4-isopropyl-2-methoxyphenyl)-1,3-dioxo-2,3-dihydro-1H-inden-2,4-diyl)diacetamide(200 mg, 0.49 mmol) in dichloromethane (10 ml) was dropwise added over10 min, and stirred at room temperature for 12 hrs. The reaction mixturewas poured with water, extracted with dichloromethane, and purified bysilica gel column chromatography (ethyl acetate:hexane=2:1) to affordthe title compound. 130 mg (67%).

mp: 205-207° C.

¹H-NMR (300 MHz, CDCl₃) δ 1.15 (d, J=6.9 Hz, 6H, CH₃) 1.98 (s, 3H, NAc)2.19 (s, 3H, NAc) 2.8 (septet, J=6.9 Hz, 1H, CH) 5.61 (s, 1H, OH) 6.61(s, 1H, NH) 6.68 (d, J=1.2 Hz, 1H, ArH) 6.82 (dd, J=1.2 Hz, J=7.8 Hz,1H, ArH) 7.28 (d, J=7.8 Hz, 1H, ArH) 7.55 (dd, J=0.6 Hz, J=7.8 Hz, 1H,ArH) 7.66-7.72 (m, 1H, ArH) 8.50 (d, J=8.4 Hz, 1H, ArH) 10.03 (s, 1H,NH). MS(EI): 394.

Step 2: 4b,5,9b,10-tetrahydroindeno[2,1-a]inden-4b-ol

Chrome chloride (2.50 g, 16.00 mmol) and nickel chloride (130 mg, 1mmol) were dissolved in dimethylformamide (25 ml), and stirred at roomtemperature for 10 min. The resulting solution was reacted with asolution of 1-(2-bromobenzyl)-1H-inden-2(3H)-one (2.50 g, 0.83 mmol) indimethylformamide (25 ml) at 120-125° C. for 18 hrs. The reactionmixture was poured with water, extracted with diethyl ether, andpurified by silica gel column chromatography (ethylacetate:hexane=1:10)to afford the title compound. 0.30 g (16%).

¹H-NMR (300 MHz, CDCl₃) δ 2.05 (s, 1H, OH) 3.05 (dd, J=1.5 Hz, J=16.2Hz, 1H) 3.56 (d, J=2.4 Hz, 2H) 3.59-3.67 (m, 1H, CH) 3.87 (d, J=7.8 Hz,1H) 7.11-7.26 (m, 7H, ArH) 7.51-7.53 (m, 1H, ArH)

Step 3: 5,10-dihydroindeno[2,1-a]indene

4b,5,9b,10-tetrahydroindeno[2,1-a]inden-4b-ol (0.10 g, 0.82 mmol) wasdissolved in benzene (5 ml) and added a little amount of paratoluenesulfonyl acid at room temperature. The reaction mixture was refluxed 85°C. for 12 hrs to completely evaporate benzene, and the residue wasseparated using silica gel column chromatography (2% ethyl acetate inhexane) to afford the title compound as a solid. 45 mg (50%).

¹H-NMR (300 MHz, CDCl₃) δ 3.63 (s, 4H, CH₂) 7.16-7.34 (m, 4H, ArH)7.42-7.53 (m, 4H, ArH).

Step 4: (4b,9b)-4b,5,9b,10-tetrahydroindeno[2,1-a]indene-4b,9b-diol

Osmium tetroxide (0.02 ml, 0.002 mmol, 2.5% in t-butanol), potassiumferricyanide (193 mg, 0.6 mmol), potassium carbonate (81 mg, 0.6 mmol),and quinolidine (2.2 mg, 0.02 mmol) were mixed in a mixture of t-butanoland water (1:1, 3 ml) to which a solution of methane sulfonamide (19 mg,0.2 mmol) and 5,10-dihydroindeno[2,1-a]indene (40 mg, 0.2 mmol) in 1 mlof a mixture of t-butanol and water (1:1) was then added.

The resulting mixture was stirred for 4.5 hrs at room temperature andthen added with sodium sulfite (0.2 g) and stirred for an additional 15min. The reaction mixture was poured with water, extracted with diethylether, concentrated, and purified by silica gel column chromatography(ethyl acetate:hexane=1:2) to afford the title compound. White 25 mg(54%).

mp: 157-159° C.

¹H-NMR (300 MHz, CDCl₃) δ 2.89 (s, 2H, OH) 3.40 (q, J=16.8 Hz, J=8.4 Hz,4H, CH₂) 7.13-7.28 (m, 6H, ArH) 7.50-7.53 (m, 2H, ArH). MS(EI): 238.

<Example 88>4b,9b-Dihydroxy-7-isopropyl-4bH-indeno[1,2-b]benzofuran-10(9bH)-oneO-methyl oxime

To a solution of4b,9b-dihydroxy-7-isopropyl-4bH-indeno[1,2-b]benzofuran-10(9bH)-one(1.00 g, 3.37 mmoels) in anhydrous pyridine (1 ml) was added O-methylhydroxylamine hydrochloride (564 mg, 6.75 mmoles), followed by reactionat room temperature for 3 hrs while stirring. After removal of thesolvent pyridine, extraction with DCM and water was conducted, and theconcentrated organic layer was separated and purified by silica gelcolumn chromatography (30% ethylacetate mixed with 30% hexane) to affordthe title compound. 70 mg (30%).

¹H-NMR (300 MHz, DMSO) δ 1.17 (d, J=6.9 Hz, 6H, CH₃) 2.79 (septet, J=6.9Hz, 1H, CH) 3.9 (s, 3H, N—OCH₃), 6.44 (s, 1H, ArH/OH), 6.64 (s, 1H, ArH)6.75 (d, J=7.8 Hz, 1H, ArH) 7.54 (d, J=7.8 Hz, 1H, ArH) 7.71-7.76 (m,1H, ArH) 7.84-7.88 (m, 2H, ArH) 8.40 (d, J=8.1 Hz, 1H, ArH) 9.25 (s, 1H,OH/NH).

<Example 89> Butyric acid9b-butyrylamino-7-isopropyl-10-oxo-9b,10-dihydro-5-oxa-indeno[2,1-a]inden-4b-ylester

To a solution of9b-amino-4b-hydroxy-7-isopropyl-4b,9b-dihydro-5-oxa-indeno[2,1-a]inden-10-one(0.20 g, 0.67 mmol) in anhydrous methylene chloride (10 ml) were addedtriethylamine (0.20 g, 2.01 mmol) and butyryl chloride (0.18 g, 1.69mmol) at room temperature, followed by reaction for 3 hrs at roomtemperature while stirring. The reaction product was concentrated, andextracted with ethylacetate, after which the concentrated organic layerwas purified using column chromatography (ethylacetate:hexane=1:4 to1:2) to afford the title compound. 50 mg (17%).

¹H-NMR (300 MHz, CDCl₃) δ 0.90-1.00 (m, 6H, CH₃) 1.18 (dd, J=2.7, 6.9Hz, 6H, CH₃) 1.50-1.72 (m, 4H, CH₂) 2.02-2.30 (m, 2H, CH₂) 2.33-2.54 (m,2H, CH₂) 2.79-2.88 (m, 1H, CH) 6.00 (s, 1H, NH) 6.67 (s, 1H, ArH) 6.90(d, J=8.1 Hz, 1H, ArH) 7.44 (d, J=7.8 Hz, 1H, ArH) 7.56 (t, J=7.5 Hz,1H, ArH) 7.76 (t, J=7.5 Hz, 1H, ArH) 7.85 (d, J=7.8 Hz, 1H, ArH) 7.93(d, J=7.8 Hz, 1H, ArH).

<Example 90> Octanoic acid[2-(2-hydroxy-4-isopropyl-phenyl)-1,3-dioxo-indan-2-yl]-amide

To a solution of9b-amino-4b-hydroxy-7-isopropyl-4b,9b-dihydro-5-oxa-indeno[2,1-a]inden-10-one(0.20 g, 0.67 mmol) in anhydrous methylene chloride (10 ml) were addedtriethylamine (0.20 g, 2.01 mmol) and octanoyl chloride (0.27 g, 1.67mmol), followed by reacting at room temperature for 28 hrs whilestirring. The reaction product was concentrated, and extracted withethylacetate, after which the concentrated organic layer was purifiedusing column chromatography (ethylacetate:hexane=1:6→1:4) to afford thetitle compound as a syrup. 0.13 g (45%).

¹H-NMR (300 MHz, CDCl₃) δ 0.84-0.88 (m, 3H, CH₃) 1.17 (dd, J=3.0, 6.9Hz, 6H, CH₃) 1.26-1.29 (m, 12H, CH₂) 1.58-1.65 (m, 4H, CH₂) 2.31 (t,J=7.2 Hz, 2H, CH₂) 2.77-2.86 (m, 1H, CH) 5.71 (s, 1H, OH) 6.62 (s, 1H,NH) 6.71 (s, 1H, ArH) 6.81 (d, J=7.8 Hz, 1H, ArH) 7.24 (d, J=7.8 Hz, 1H,ArH) 7.55 (t, J=7.8 Hz, 1H, ArH) 7.78-7.84 (m, 2H, ArH) 8.00 (d, J=7.8Hz, 1H, ArH).

<Example 91> Hexanoic acid9b-hexanoylamino-7-isopropyl-10-oxo-9b,10-dihydro-5-oxa-indeno[2,1-a]inden-4b-ylester

To a solution of9b-amino-4b-hydroxy-7-isopropyl-4b,9b-dihydro-5-oxa-indeno[2,1-a]inden-10-one(0.20 g, 0.67 mmol) in anhydrous methylene chloride (10 ml) were addedtriethylamine (0.20 g, 2.01 mmol), and hexanoyl chloride (0.22 g, 1.69mmol), followed by reaction for 5 hrs at room temperature whilestirring. The reaction product was concentrated, and extracted withethylacetate, after which the concentrated organic layer was purifiedusing column chromatography (ethylacetate:hexane=1:6 to 1:4) to affordthe title compound. 15 mg (4%).

¹H-NMR (300 MHz, CDCl₃) δ 0.79-0.89 (m, 6H, CH₃) 1.17 (dd, J=2.7, 6.9Hz, 6H, CH₃) 1.22-1.33 (m, 8H, CH₂) 1.40-1.65 (m, 4H, CH₂) 2.04-2.55 (m,4H, CH₂) 2.82-2.91 (m, 1H, CH) 6.00 (s, 1H, NH) 6.67 (s, 1H, ArH) 6.91(d, J=8.1 Hz, 1H, ArH) 7.44 (d, J=8.1 Hz, 1H, ArH) 7.56 (t, J=7.5 Hz,1H, ArH) 7.74-7.89 (m, 2H, ArH) 7.93 (d, J=7.5 Hz, 1H, ArH).

<Example 92> Heptanoic acid9b-heptanoylamino-7-isopropyl-10-oxo-9b,10-dihydro-5-oxa-indeno[2,1-a]inden-4b-ylester

Triethylamine (0.20 g, 2.01 mmol), and heptanoyl chloride (0.25 g, 1.69mmol) were added at room temperature to a solution of9b-amino-4b-hydroxy-7-isopropyl-4b,9b-dihydro-5-oxa-indeno[2,1-a]inden-10-one(0.20 g, 0.67 mmol) in anhydrous methylene chloride (10 ml), and stirredfor 3 hrs. The reaction product was concentrated, and extracted withethylacetate, after which, the concentrated organic layer was purifiedusing column chromatography (ethylacetate:hexane=1:6 to 1:4) to affordthe title compound. 0.14 g (40%).

¹H-NMR (300 MHz, CDCl₃) δ 0.84-0.88 (m, 6H, CH₃) 1.17 (dd, J=2.4, 6.9Hz, 6H, CH₃) 1.25-1.44 (m, 14H, CH₂) 1.59-1.64 (m, 2H, CH₂) 2.06-2.52(m, 4H, CH₂) 2.79-2.86 (m, 1H, CH) 5.98 (s, 1H, NH) 6.74 (s, 1H, ArH)6.91 (d, J=7.8 Hz, 1H, ArH) 7.44 (d, J=8.1 Hz, 1H, ArH) 7.56 (t, J=7.5Hz, 1H, ArH) 7.76 (t, J=7.5 Hz, 1H, ArH) 7.85 (d, J=7.8 Hz, 1H, ArH)7.92 (d, J=7.5 Hz, 1H, ArH).

<Example 93>N-((4bS,9bS)-1-Amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)octanamide

N-(4b-hydroxy-7-isopropyl-1-nitro-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)octanamide(130 mg, 0.28 mmoles) was dissolved in ethanol:water (9:1, 13 mL), addedwith iron powder (118 mg, 2.12 mmoles) and conc. HCl (3 drops), andheated for 3 hrs under reflux. After the reaction mixture was filtered,the filtrate was concentrated in a vacuum, and isolated and purified bysilica gel column chromatography (30% ethylacetate, 1% triethylamine inhexane) to afford the title compound. 115 mg (96%).

¹H-NMR (300 MHz, CDCl₃) δ 0.86 (t, J=6.6 Hz, 3H, CH₃) 1.17 (d, J=6.9 Hz,6H, CH₃) 1.25 (m, 8H, CH₂) 1.59 (t, J=6.9 Hz, 2H, CH₂) 2.51 (t, J=6.9Hz, 2H, CH₂) 2.81 (septet, J=6.9 Hz, 1H, CH) 5.66 (br, 2H, NH₂) 6.62 (m,2H, ArH) 6.73-6.79 (m, 2H, ArH) 7.13-7.16 (m, 1H, ArH) 7.39-7.45 (t,J=7.8 Hz, 1H, ArH).

<Example 94>(4bR,9bS)-1-Amino-7-isopropyl-10-oxo-9b-propionamido-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-4b-ylpropionate

(4bR,9bS)-7-isopropyl-1-nitro-10-oxo-9b-propionamido-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-4b-ylpropionate (130 mg, 0.29 mmoles) was dissolved in ethanol:water (9:1, 10mL), added with iron powder (122 mg, 2.18 mmoles), and conc. HCl (3drops), and heated for 1 hr under reflux. After the reaction mixture wasfiltered, the filtrate was concentrated in a vacuum, and isolated andpurified by silica gel column chromatography (30% ethylacetate, 1%triethylamine in hexane) to afford the title compound. 60 mg (50%).

¹H-NMR (300 MHz, CDCl₃) δ 1.05-1.20 (m, 12H, CH₃) 2.10-2.51 (m, 4H, CH₂)2.85 (septet, J=6.9 Hz, 1H, CH) 4.41 (br, 2H, NH₂) 5.99 (br, 1H, NH)6.73 (s, 1H, ArH) 6.89-6.96 (m, 2H, ArH) 7.22-7.34 (m, 2H, ArH) 7.43 (d,J=7.8 Hz, 1H, ArH).

<Example 95>(4bR,9bS)-1-Amino-9b-butyramido-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-4b-ylbutyrate

(4bR,9bS)-9b-Butyramido-7-isopropyl-1-nitro-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-4b-ylbutyrate (220 mg, 0.46 mmoles) was dissolved in ethanol:water (9:1, 10mL), added with iron powder (195 mg, 3.48 mmoles) and conc. HCl (5drops), and heated for 1 hr under reflux. After the reaction mixture wasfiltered, the filtrate was concentrated in a vacuum, and isolated andpurified by silica gel column chromatography (30% ethylacetate, 1%triethylamine in hexane) to afford the title compound. 100 mg (49%).

¹H-NMR (300 MHz, CDCl₃) δ 0.90-0.99 (m, 6H, CH₃) 1.16-1.19 (m, 6H, CH₃)1.50-1.77 (m, 4H, CHO 2.04-2.50 (m, 4H, CH₂) 2.85 (septet, J=6.9 Hz, 1H,CH) 4.40 (br, 2H, NH₂) 5.97 (br, 1H, NH) 6.71 (s, 1H, ArH) 6.71-6.97 (m,2H, ArH) 7.22-7.35 (m, 2H, ArH) 7.41 (d, J=8.1 Hz, 1H, ArH).

<Example 96>1-Amino-7-isopropyl-10-oxo-9b-pentanamido-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-4b-ylpentanoate

To a solution of7-isopropyl-1-nitro-10-oxo-9b-pentanamido-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-4b-ylpentanoate (0.287 g, 0.55 mmol) in ethanol (10 ml) were added 1 ml ofwater, iron powder (0.22 g, 4.01 mmol), and conc. HCl (0.05 ml),followed by heating for 1.5 hrs under reflux. After the reaction mixturewas filtered, the filtrate was concentrated in a vacuum, and isolatedand purified by column chromatography (ethylacetate:hexane=1:4 to 1:2)to afford the title compound. 0.12 g (46%).

¹H-NMR (300 MHz, CDCl₃) δ 0.89 (m, 6H, CH₃) 1.17 (dd, J=2.4, 6.9 Hz, 6H,CH₃) 1.23-1.48 (m, 4H, CHO 1.50-1.65 (m, 4H, CH₂) 2.04-2.37 (m, 2H, CH₂)2.40-2.54 (m, 2H, CH₂) 2.80-2.89 (m, 1H, CH) 4.39 (s, 2H, NH₂) 5.91 (s,1H, NH) 6.71 (s, 1H, ArH) 6.88-6.96 (m, 2H, ArH) 7.22-7.34 (m, 2H, ArH)7.46 (d, J=8.1 Hz, 1H, ArH).

<Example 97>1-amino-9b-hexanamido-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-4b-ylhexanoate

9b-Hexanamido-7-isopropyl-1-nitro-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-4b-ylhexanoate (0.17 g, 0.32 mmol) was dissolved in ethanol (15 ml), addedwith 1.5 ml of water, iron powder (0.13 g, 2.3 mmol), and conc. HCl(0.05 ml), and heated for 1 hr under reflux. After the reaction mixturewas filtered, the filtrate was concentrated in a vacuum, and isolatedand purified by column chromatography (ethylacetate:hexane=1:6 to 1:4)to afford the title compound. 0.15 g (90%).

¹H-NMR (300 MHz, CDCl₃) δ 0.77-0.93 (m, 6H, CH₃) 1.20 (dd, J=3.6, 6.9Hz, 6H, CH₃) 1.23-1.39 (m, 8H, CH₂) 1.50-1.62 (m, 4H, CH₂) 2.04-2.51 (m,4H, CHO 2.80-2.86 (m, 1H, CH) 4.40 (s, 2H, NH₂) 5.97 (s, 1H, NH) 6.72(s, 1H, ArH) 6.88-7.06 (m, 2H, ArH) 7.22-7.34 (m, 2H, ArH) 7.43 (d,J=7.6 Hz, 1H, ArH).

<Example 98>(4bS,9bS)-4b-Hydroxy-7-isopropyl-9b-methoxy-4bH-indeno[1,2-b]benzofuran-10(9bH)-one

Anhydrous methanol (0.1 mL) was slowly added at 0° C. over 5 min to asolution of(4bS,9bS)-9b-chloro-4b-hydroxy-7-isopropyl-4bH-benzo[d]indeno[1,2-b]furan-10(9bH)-one(0.30 g, 0.95 mmoles) in anhydrous THF (10 ml). After reaction for 3hrs, the reaction mixture was concentrated, and isolated and purified bysilica gel column chromatography (30% ethylacetate in 20% hexane) toafford the title compound. 50 mg (17%).

¹H-NMR (300 MHz, CDCl₃) δ 1.18 (dd, J=2.4 Hz, J=6.9 Hz, 6H, CH₃) 2.84(septet, J=6.9 Hz, 1H, CH) 3.70 (s, 3H, OCH₃) 4.51 (s, 1H, OH) 6.72 (s,1H, ArH) 6.85 (dd, J=1.2 Hz, J=7.8 Hz, 1H, ArH) 7.49 (d, J=7.8 Hz, 1H,ArH) 7.52-7.58 (m, 1H, ArH) 7.77-7.82 (m, 2H, ArH) 7.98 (d, J=7.8 Hz,1H, ArH).

<Example 99>1-Amino-9b-heptanamido-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-4b-ylheptanoate

9b-Heptanamido-7-isopropyl-1-nitro-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-4b-ylheptanoate (0.28 g, 0.50 mmol) was dissolved in ethanol (10 ml), addedwith 1 ml of water, iron powder (0.20 g, 3.7 mmol), and conc. HCl (0.05ml), and heated for 1 hr under reflux. After the reaction mixture wasfiltered, the filtrate was concentrated in a vacuum, and purified bycolumn chromatography (ethylacetate:hexane=1:6 to 1:4) to afford thetitle compound. 0.15 g (90%).

¹H-NMR (300 MHz, CDCl₃) δ 0.79-0.97 (m, 6H, CH₃) 1.19 (dd, J=3.7, 6.9Hz, 6H, CH₃) 1.25-1.39 (m, 12H, CH₂) 1.59-1.68 (m, 2H, CH₂) 2.08-2.30(m, 4H, CH₂) 2.36-2.54 (m, 2H, CH₂) 2.84-2.89 (m, 1H, CH) 4.42 (s, 2H,NH₂) 5.98 (s, 1H, NH) 6.74 (s, 1H, ArH) 6.91-6.98 (m, 2H, ArH) 7.24-7.37(m, 2H, ArH) 7.43 (d, J=7.8 Hz, 1H, ArH).

<Example 100>1-((4bS,9bS)-7-Isopropyl-4b-methoxy-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)urea

Conc. HCl (1 mL) was added to a solution of(4bS,9bR)-7-isopropyl-10H-4b,9b-(epiminomethanoimino)indeno[1,2-b]benzofurane-10,12-dione(0.20 g, 0.625 mmoles) in methanol (10 mL) and stirred at roomtemperature. After reaction for 2.5 hrs, the reaction mixture wasconcentrated, extracted with ethylacetate and water, and thenconcentrated in a vacuum to dryness. Purification through silica gelcolumn chromatography (5% MeOH in DCM, 1% TEA) afforded the titlecompound. (80 mg, 38%).

¹H-NMR (300 MHz, CD₃OD) δ 1.17 (d, J=6.9 Hz, 6H, CH₃) 2.75 (sept, J=6.9Hz, 1H, CH) 3.68 (s, 3H, CH₃) 6.50 (dd, J=1.2 Hz, J=7.8 Hz, 1H, ArH)6.68 (s, 1H, ArH) 6.76 (d, J=7.8 Hz, 1H, ArH) 7.35-7.53 (m, 3H, ArH)7.83 (d, J=7.5 Hz, 1H, ArH).

<Example 101>1-((4bS,9bS)-4b-Hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-3-methylurea

To a solution of(4bS,9bS)-9b-amino-4b-hydroxy-7-isopropyl-4bH-benzo[d]indeno[1,2-b]furan-10(9bH)-one(0.10 g, 0.34 mmoles) in anhydrous THF (2 ml was added methyl isocyanate(32 μL, 0.51 mmoles). After reaction for 1 hr, the reaction mixture wasconcentrated and purified by silica gel column chromatography (5% MeOHin DCM, 1% TEA) to afford the title compound. 50 mg (42%).

¹H-NMR (300 MHz, CDCl₃) δ 1.20 (d, J=6.9 Hz, 6H, CH₃) 2.78-2.89 (m, 4H,NMe, CH) 6.63 (s, 1H, ArH) 6.86 (dd, J=1.2 Hz, J=7.8 Hz, 1H, ArH) 7.43(d, J=7.8 Hz, 1H, ArH) 7.56 (br, 2H, ArH) 7.81 (br, 2H, ArH).

<Example 102>1-Ethyl-3-((4bS,9bS)-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)urea

To a solution of(4bS,9bS)-9b-amino-4b-hydroxy-7-isopropyl-4bH-benzo[d]indeno[1,2-b]furan-10(9bH)-one(0.10 g, 0.34 mmoles) in anhydrous THF (5 ml) was added ethyl isocyanate(45 μL, 0.85 mmoles). After reaction for 1 hr, the reaction mixture wasconcentrated and purified by silica gel column chromatography (5% MeOHin DCM, 1% TEA) to afford the title compound. 60 mg (19%).

¹H-NMR (300 MHz, CDCl₃) δ 1.04 (t, J=7.2 Hz, 3H, CH₃) 1.20 (dd, J=2.4Hz, J=6.9 Hz, 6H, CH₃) 2.84 (septet, J=6.9 Hz, 1H, CH) 3.36-3.51 (m, 2H,CH₂ 6.62 (d, J=1.2 Hz, 1H, ArH) 6.85 (dd, J=1.2 Hz, J=8.1 Hz, 1H, ArH)7.46 (d, J=8.1 Hz, 1H, ArH) 7.52-7.62 (m, 2H, ArH) 7.68-7.70 (m, 1H,ArH), 7.77-7.98 (m, 1H, ArH).

<Example 103>1-((4bS,9bS)-4b-Hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-3-methoxyurea

Boron tribromide (1.0 M solution in DCM, 1.72 mL, 1.72 mmoles) wasdissolved in anhydrous DCM (10 ml) and cooled to −80° C. To this, asolution of1-(2-(4-isopropyl-2-methoxyphenyl)-1,3-dioxo-2,3-dihydro-1H-inden-2-yl)-3-methoxyurea(300 mg, 0.78 mmoles) in anhydrous DCM (15 ml) was slowly added. Thereaction mixture was maintained for 10 min at −80° C. and stirred for 3hrs at 0° C. Thereafter, the reaction mixture was extracted with DCM andwater, dried, and concentrated in a vacuum. Purification through silicagel column chromatography (5% MeOH in DCM, 1% TEA) afforded the titlecompound. 110 mg (38%).

¹H-NMR (300 MHz, CDCl₃) δ 1.20 (d, J=6.9 Hz, 6H, CH₃) 2.83 (septet,J=6.9 Hz, 1H, CH) 3.88 (s, 3H, OCH₃) 6.64 (d, J=1.2 Hz, 1H, ArH) 6.85(dd, J=1.2 Hz, J=7.8 Hz, 1H, ArH) 7.37 (d, J=7.8 Hz, 1H, ArH) 7.55-7.60(m, 1H, ArH) 7.66-7.71 (m, 1H, ArH), 7.78-7.84 (m, 2H, ArH).

<Example 104>5-Acetyl-4b,9b-dihydroxy-7,8-dimethyl-4b,5-dihydroindeno[1,2-b]indol-10(9bH)-one

N-(3,4-dimethylphenyl)acetamide (300 mg, 1.84 mmol) and ninhydrin (328mg, 1.84 mmol) were dissolved in dil. sulfuric acid (6 mL) and stirredat room temperature for 5.5 hrs. The reaction was stopped by slowingpouring the solution to 150 g of ice and stirring. The reaction mixturewas washed twice with ethylacetate (70 ml), and the organic layer waswashed again with water and brine. It was dried over sodium sulfate,concentrated in a vacuum, and purified through column chromatography(ethylacetate:hexane=1:1), followed by recrystallization inethylacetate/hexane to afford the title compound. 60 mg (10%).

¹H-NMR (300 MHz, DMSO) δ 2.13 (s, 6H, CH₃) 2.74 (s, 3H, NAc) 6.84 (s,1H, ArH) 7.16 (s, 1H, ArH) 7.49 (br, 1H, ArH) 7.56-7.61 (m, 1H, ArH)7.63-7.71 (m, 1H, ArH) 7.80-7.89 (m, 2H, ArH) 8.01-8.05 (m, 1H, ArH).

<Example 105>4b,9b-Dihydroxy-7,8-dimethyl-5-propionyl-4b,5-dihydroindeno[1,2-b]indol-10(9bH)-one

Ten drops of conc. HCl were added to a solution ofN-(2-(2-hydroxy-1,3-dioxo-2,3-dihydro-1H-inden-2-yl)-4,5-dimethylphenyl)propionamide(0.20 g) in anhydrous THF (10 ml) and stirred. After reaction for 5 hrs,ice water was poured to stop the reaction. Extraction with ethylacetateand water was conducted before concentration in a vacuum. Theconcentrate was purified by column chromatography (30% ethylacetatemixed with 50% hexane) to afford the title compound. 40 mg (20%).

¹H-NMR (300 MHz, DMSO) δ 1.26 (t, J=7.5 Hz, 3H, CH₃) 2.14 (s, 6H, CH₃)3.06-3.58 (m, 2H, CH₂) 6.84 (s, 1H, ArH/OH) 7.16 (s, 1H, ArH/OH) 7.48(s, 1H, ArH/OH) 7.56-7.61 (m, 1H, ArH) 7.70 (d, J=7.8 Hz, 1H, ArH)7.80-7.86 (m, 2H, ArH) 7.95-8.01 (m, 1H, ArH).

<Example 106>4b,9b-Dihydroxy-7,8-dimethyl-4b,5-dihydroindeno[1,2-b]indol-10(9bH)-one

Conc. HCl (1 ml) was added to a solution ofN-(2-(2-hydroxy-1,3-dioxo-2,3-dihydro-1H-inden-2-yl)-4,5-dimethylphenyl)acetamide(0.10 g) in methanol (10 ml) and stirred overnight to concentration. Theconcentrate was washed with sat. NaHCO₃, extracted with ethylacetate andwater, and concentrated in a vacuum to afford the title compound (50 mg,58%).

¹H-NMR (300 MHz, DMSO) δ 2.33 (s, 3H, CH₃) 2.36 (s, 3H, CH₃) 7.30 (s,1H, ArH) 7.49 (s, 1H, ArH) 7.55 (t, J=7.8 Hz, 1H, ArH) 7.94 (t, J=7.8Hz, 1H, ArH) 8.03 (d, J=7.8 Hz, 1H, ArH) 8.25 (d, J=7.8 Hz, 1H, ArH)11.70 (br, 1H, NH).

<Example 107>5-Acetyl-7,8-dimethyl-10-oxo-4b,5,9b,10-tetrahydroindeno[1,2-b]indole-4b,9b-diyldiacetate

Acetyl chloride (0.33 mL, 4.64 mmoles), and triethylamine (0.65 mL, 4.64mmoles) were slowly added at room temperature to a solution of5-acetyl-4b,9b-dihydroxy-7,8-dimethyl-4b,5-dihydroindeno[1,2-b]indol-10(9bH)-one(300 mg, 0.93 mmol) in anhydrous THF (20 mL). After stirring at roomtemperature for 24 hrs, the solid thus formed was washed with THF andfiltered. After removal of THF, purification through columnchromatography (30% ethylacetate mixed with 30% hexane) afford the titlecompound as a yellowish solid. 150 mg (40%).

¹H-NMR (300 MHz, DMSO) δ 2.06 (s, 3H, OAc) 2.10 (s, 3H, OAc) 2.22-2.23(s, 6H, CH₃) 2.47 (s, 3H, NAc) 7.23 (s, 1H, ArH) 7.37 (s, 1H, ArH)7.64-7.69 (t, 1H, ArH) 7.75 (d, J=7.2 Hz, 1H, ArH) 7.87-7.92 (m, 1H,ArH), 8.33 (d, J=7.8 Hz, 1H, ArH).

<Example 108>5-Acetyl-9b-amino-4b-hydroxy-5,9b-dihydro-4bH-indeno[1,2-b]indol-10-one

AIBN (0.1 g) and SO₂Cl₂ (0.72 g, 5.3 mmol) were added to a solution ofN-[2-(1,3-dioxo-indan-2-yl)-phenyl]-acetamide (1.00 g, 3.5 mmol) in CCl₄(20 ml) and heated for 3 hrs under reflux. The solution was concentratedin a vacuum, extracted with CH₂Cl₂, dried, filtered, and theconcentrated in a vacuum. Purification through column chromatography(ethylacetate:hexane=1:4→1:2) afforded the title compound. 0.60 g (53%).

¹H-NMR (300 MHz, CDCl₃) δ 2.64 (s, 3H, CH₃) 7.19 (t, J=1.5, 8.4 Hz, 1H,ArH) 7.37 (t, J=1.5, 8.4 Hz, 1H, ArH) 7.55 (t, J=7.2 Hz, 1H, ArH)7.73-7.83 (m, 3H, ArH) 8.20 (d, J=8.1 Hz, 1H, ArH).

<Example 109>N-(9b-Amino-4b-hydroxy-7-isopropyl-4-nitro-10-oxo-9b,10-dihydro-4bH-5-oxa-indeno[2,1-a]inden-1-yl)-acetamide

To a solution ofN-(9b-chloro-4b-hydroxy-7-isopropyl-4-nitro-10-oxo-9b,10-dihydro-4bH-5-oxa-indeno[2,1-a]inden-1-yl)-acetamide(3.90 g, 9.3 mmol) in anhydrous THF (40 ml) was added 2M NH₃ in IPA(9.36 ml) at 5° C., followed by stirring overnight at room temperature.After removal of the solvent by concentration in a vacuum, the residuewas diluted in methylene chloride and washed with an aqueous sodiumbicarbonate solution to adjust the pH into 8.0. The organic layer wasdried, filtered and concentrated in a vacuum to afford the titlecompound. 3.98 g (107%).

¹H-NMR (300 MHz, CDCl₃) δ 1.16 (dd, J=6.9, 2.7 Hz, 6H, CH₃) 2.29 (s, 3H,CH₃) 2.78-2.87 (sept, 1H, CH) 6.71 (s, 1H, ArH) 6.88 (dd, J=8.1, 2.1 Hz,1H, ArH) 7.37 (d, J=7.8 Hz, 1H, ArH) 8.48 (d, J=9.3 Hz, 1H, ArH) 8.75(d, J=9.3 Hz, 1H, ArH) 10.67 (s, 1H, NH).

<Example 110> Acetic acid1,9b-bis-acetylamino-7-isopropyl-4-nitro-10-oxo-9b,10-dihydro-5-oxa-indeno[2,1-a]inden-4b-ylester

To a solution ofN-(9b-amino-4b-hydroxy-7-isopropyl-4-nitro-10-oxo-9b,10-dihydro-4bH-5-oxa-indeno[2,1-a]inden-1-yl)-acetamide(0.55 g, 1.38 mmol) in anhydrous methylene chloride (20 ml) were addedtriethylamine (0.21 g, 2.76 mmol) and AcCl (0.20 g, 2.07 mmol) at 0° C.,followed by stirring overnight at room temperature. The reaction mixturewas concentrated in a vacuum and purified by column chromatography(ethylacetate:hexane=1:4) to afford the title compound. 0.17 g (26%).

¹H-NMR (300 MHz, CDCl₃) δ 1.19 (dd, J=3.6, 6.9 Hz, 6H, CH₃) 2.00 (s, 3H,CH₃) 2.17 (s, 3H, CH₃) 2.25 (s, 3H, CH₃) 2.83-2.92 (m, 1H, CH) 6.15 (s,1H, NH) 6.71 (s, 1H, ArH) 6.98 (d, J=7.8 Hz, 1H, ArH) 7.43 (d, J=7.8 Hz,1H, ArH) 8.50 (d, J=9.0 Hz, 1H, ArH) 8.83 (d, J=9.3 Hz, 1H, ArH) 10.72(s, 1H, NH).

<Example 111>9b-Acetamido-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-4b-ylmethyl carbonate

ToN-(4b-Hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)acetamide(0.50 g, 1.48 mmol were added 10 ml of THF, Et₃N (0.24 ml, 1.77 mmol,and methyl chloroformate (0.11 ml, 1.48 mmol in that order, after whichthe solution was stirred at room temperature for 12 hrs.

The reaction mixture was concentrated, extracted with H₂O and CH₂Cl₂,and purified by column chromatography (ethylacetate:hexane=1:2) toafford the title compound. 20 mg (3%).

¹H-NMR (300 MHz, CDCl₃) δ 1.16 (d, J=2.6 Hz, 3H), 1.18 (d, J=2.6 Hz,3H), 2.17 (s, 3H), 2.84 (q, J=7.8 Hz, 1H), 3.62 (s, 3H), 5.40 (s, 1H),6.68 (s, 1H), 6.91 (d, J=7.7 Hz, 1H), 7.44 (d, J=8.1 Hz, 1H), 7.58 (t,J=8.5 Hz, 1H), 7.78 (t, J=8.1 Hz, 1H), 7.87 (d, J=7.7 Hz, 1H), 7.98 (d,J=8.1 Hz, 1H).

<Example 112>9b-Acetamido-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-4b-ylpentanoate

ToN-(4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)acetamide(0.50 g, 1.48 mmol were added 10 ml of THF, Et₃N (0.24 ml, 1.77 mmol,and valeroyl chloride (0.18 ml, 1.48 mmol in that order, followed bystirring the solution at room temperature for 12 hrs. Afterconcentration, the concentrate was extracted with H₂O and CH₂Cl₂ andpurified by column chromatography (ethylacetate:hexane=1:2) to affordthe title compound. (30 mg, 5%).

¹H-NMR (300 MHz, CDCl₃) δ 0.91 (t, J=7.4 Hz, 3H), 1.16 (d, J=2.6 Hz,3H), 1.18 (d, J=2.6 Hz, 3H), 1.33-1.40 (m, 2H), 1.56-1.64 (m, 2H), 1.95(s, 3H), 2.35-2.55 (m, 2H), 2.84 (q, J=7.6 Hz, 1H), 6.10 (s, 1H), 6.68(d, J=0.9 Hz, 1H), 6.91 (dd, J=1.3 Hz, 7.8 Hz, 1H), 7.44 (d, J=8.0 Hz,1H), 7.57 (t, J=8.0 Hz, 1H), 7.77 (t, J=8.2 Hz, 1H) 7.84 (d, J=7.5 Hz,1H), 7.93 (d, J=7.8 Hz, 1H).

<Example 113>9b-acetamido-1-amino-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-4b-ylmethyl carbonate

To9b-acetamido-7-isopropyl-1-nitro-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-4b-ylmethyl carbonate (50 mg, 0.11 mmol) were added EtOH:H₂O=2 ml:0.2 ml, Fe(40 mg, 0.79 mmol, and one drop of conc. HCl, followed by reflux for 1hr.

After neutralization with NaHCO₃, the reaction mixture was purified bycolumn chromatography (ethylacetate:hexane=1:1) to afford the titlecompound. (25 mg, 55%).

¹H-NMR (300 MHz, CDCl₃) δ 1.17 (d, J=2.6 Hz, 3H), 1.19 (d, J=2.6 Hz,3H), 2.18 (s, 3H), 2.85 (q, J=7.7 Hz, 1H), 3.63 (s, 3H), 4.44 (s, 2H),6.72 (s, 2H), 6.90 (d, J=7.8 Hz, 1H), 6.97 (d, J=7.7 Hz, 1H), 7.23-7.25(m, 1H), 7.34 (d, J=7.9 Hz, 1H), 7.41 (d, J=7.9 Hz, 1H).

<Example 114>N-(1-Amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)pivalamide

Iron powder (0.04 g, 0.85 mmol), conc. HCl (0.05 ml), and water (0.5 ml)were added in that order to a solution ofN-(4b-hydroxy-7-isopropyl-1-nitro-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)pivalamide(50 mg, 0.11 mmol) in absolute ethanol (5 ml). The reaction mixture washeated for 2 hrs under reflux. After the iron powder was filtered off,the filtrate was concentrated in a vacuum and purified by columnchromatography (ethylacetate:hexane=1:2) to afford the title compound.(40 mg, 86%).

¹H-NMR (300 MHz, CDCl₃) δ 1.16-1.19 (m, 15H, CH₃) 2.71-2.92 (m, 1H, CH)6.66 (s, 1H, ArH) 6.81 (d, J=7.2 Hz, 1H, ArH) 6.93-7.01 (m, 2H, ArH)7.11-7.25 (m, 1H, ArH) 7.38-7.47 (m, 1H, ArH).

<Example 115>9b-Acetamido-1-amino-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-4b-ylbutyl carbonate

Iron powder (0.09 g, 1.66 mmol), conc. HCl (0.05 ml), and water (0.5 ml)were added in that order to a solution of9b-acetamido-7-isopropyl-1-nitro-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-4b-ylbutyl carbonate (0.11 g, 0.22 mmol) in absolute ethanol (5 ml). Thereaction mixture was heated for 1.5 hrs under reflux. After the ironpowder was filtered off, the filtrate was concentrated in a vacuum, andpurified by column chromatography (ethylacetate:hexane=1:2) to affordthe title compound (50 mg, 50%).

¹H-NMR (300 MHz, CDCl₃) δ 0.89 (t, J=7.5 Hz, 3H, CH₃) 1.18 (dd, J=2.4Hz, 6.9 Hz, 3H, CH₃) 1.28-1.43 (m, 2H, CH₂) 1.56-1.68 (m, 2H, CH₂) 1.96(s, 3H, CH₃) 2.81-2.90 (m, 1H, CH) 4.07-4.20 (m, 2H, OCH₂) 6.11 (s, 1H,NH) 6.76 (s, 1H, ArH) 6.94 (t, J=7.8 Hz, 2H, ArH) 7.22-7.35 (m, 2H, ArH)7.46 (d, J=7.8 Hz, 1H, ArH).

<Example 116>9b-Acetamido-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-4b-ylethyl carbonate

Ethyl chloroformate (0.32 g, 3.11 mmol) and trimethylamine (0.25 g, 2.48mmol) were added to a solution of9b-chloro-4b-hydroxy-7-isopropyl-1-nitro-4bH-benzo[d]indeno[1,2-b]furan-10(9bH)-one(0.70 g, 2.07 mmol) in anhydrous THF (15 ml), and stirred for 4 hrs.After THF was removed by concentration in a vacuum, the concentrate wasdiluted in methylene chloride and washed many times with water. Theorganic layer was dried, filtered and purified by column chromatography(ethylacetate:hexane=1:4) to afford the title compound. 14 mg (1.6%).

¹H-NMR (300 MHz, CDCl₃) δ 1.16-1.18 (m, 9H, CH₃) 2.17 (s, 3H, CH₃)2.82-2.86 (m, 1H, CH) 4.05-4.13 (m, 2H, OCH₂) 5.34 (s, 1H, NH) 6.68 (s,1H, ArH) 6.91 (d, J=7.5 Hz, 1H, ArH) 7.44 (d, J=6.9 Hz, 1H, ArH) 7.58(t, J=6.9 Hz, 1H, ArH) 7.79-7.86 (m, 2H, ArH) 7.98 (d, J=7.5 Hz, 1H,ArH).

<Example 117>9b-Acetamido-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-4b-ylpivalate

Pivaroly chloride (0.26 g, 2.22 mmol) and trimethylamine (0.18 g, 1.77mmol) were added to a solution of9b-chloro-4b-hydroxy-7-isopropyl-1-nitro-4bH-benzo[d]indeno[1,2-b]furan-10(9bH)-one(0.50 g, 1.48 mmol) in anhydrous THF (15 ml), and heated for 18 hrsunder reflux. After removal of THF by vacuum concentration, the residuewas diluted in methylene chloride and washed many times with water. Theorganic layer was dried, filtered and purified by column chromatography(ethylacetate:hexane=1:4) to afford the title compound. 0.13 g (20%).

¹H-NMR (300 MHz, CDCl₃) δ 1.16-1.19 (m, 15H, CH₃) 2.17 (s, 3H, CH₃)2.80-2.89 (m, 1H, CH) 6.11 (s, 1H, NH) 6.68 (s, 1H, ArH) 6.92 (d, J=7.8Hz, 1H, ArH) 7.45 (d, J=7.8 Hz, 1H, ArH) 7.56 (t, J=7.5 Hz, 1H, ArH)7.76 (t, J=7.5 Hz, 1H, ArH) 7.86 (d, J=7.8 Hz, 1H, ArH) 7.94 (d, J=7.8Hz, 1H, ArH).

<Example 118>9b-Acetamido-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-4b-ylmethylcarbamate

Methyl isocyanate (0.12 g, 2.22 mmol) and trimethylamine (0.18 g, 1.77mmol) were added to a solution of9b-chloro-4b-hydroxy-7-isopropyl-1-nitro-4bH-benzo[d]indeno[1,2-b]furan-10(9bH)-one(0.50 g, 1.48 mmol) in anhydrous THF (15 ml) and heated for 5 hrs underreflux. After removal of THF by vacuum concentration, the residue wasdiluted in methylene chloride and washed many times with water. Theorganic layer was dried, filtered and purified by column chromatography(ethylacetate:hexane=1:2) to afford the title compound. 0.10 g (17%).

¹H-NMR (300 MHz, CDCl₃) δ 1.17 (dd, J=2.4, 6.9 Hz, 6H, CH₃) 1.96 (s, 3H,CH₃) 2.77-2.88 (m, 4H, CH, CH₃) 5.14 (s, 1H, NH) 6.26 (s, 1H, NH) 6.70(s, 1H, ArH) 6.90 (d, J=7.8 Hz, 1H, ArH) 7.45 (d, J=7.8 Hz, 1H, ArH)7.56 (t, J=6.9 Hz, 1H, ArH) 7.75 (t, J=6.9 Hz, 1H, ArH) 7.83-7.90 (m,2H, ArH).

<Example 119>N,N′-(7-Isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofurane-4b,9b-diyldiacetamide

4b,9b-diazido-7-isopropyl-4bH-benzo[d]indeno[1,2-b]furan-10(9bH)-one(2.50 g, 7.2 mmol was dissolved in 50 ml of EtOH and stirred overnightin the presence of 10% Pd/C (0.38 g) in a hydrogen atmosphere.

The reaction mixture was filtered through a cellite layer andconcentrated in a vacuum to give4b,9b-diamino-7-isopropyl-4bH-benzo[d]indeno[1,2-b]furan-10(9bH)-one(1.60 g, 5.4 mmol. This compound was dissolved in 50 ml of THF, and Et₃N(3.02 ml, 21.7 mmol) and acetyl chloride (1.16 ml, 16.3 mmol were addedto the solution and stirred overnight at room temperature. Afterconcentration in a vacuum, the residue was purified columnchromatography (ethylacetate:hexane=2:1) to afford the title compound.0.28 g (10%).

¹H-NMR (300 MHz, CDCl₃) δ 1.14 (d, J=3.1 Hz, 3H), 1.16 (d, J=3.1 Hz,3H), 1.83 (s, 3H), 1.87 (s, 3H), 2.80 (q, J=7.6 Hz, 1H), 6.62-6.68 (m,2H), 6.83 (d, J=7.8 Hz, 1H), 7.05 (s, 1H), 7.36 (d, J=7.8 Hz, 1H), 7.54(t, J=8.7 Hz, 1H), 7.72 (t, J=8.7 Hz, 1H), 7.82 (t, J=9.5 Hz, 1H).

<Example 120>4b-(Benzyloxy)-9b-hydroxy-7-isopropyl-4bH-indeno[1,2-b]benzofuran-10(9bH)-one

p-Toluene sulfuric acid (65 mg, 0.33 mmoles) was added to a solution of4b,9b-dihydroxy-7-isopropyl-4bH-benzo[d]indeno[1,2-b]furan-10(9bH)-one(0.50 g, 1.68 mmoles) in benzylalcohol (5 mL), and stirred at 60° C. for3 days. The reaction mixture was concentrated and purified by silica gelcolumn chromatography (30% ethylacetate mixed with 10% hexane) to affordthe title compound. 20 mg (3%).

¹H-NMR (300 MHz, CDCl₃) δ 1.20 (dd, J=3 Hz, J=6.9 Hz, 6H, CH₃) 2.86(sept, J=6.9 Hz, 1H, CH) 3.42 (br, 1H, OH) 5.03 (d, J=11.4 Hz, 1H, CH₂)5.12 (d, J=11.4 Hz, 1H, CH₂) 6.76 (s, 1H, ArH) 6.90 (d, J=7.8 Hz, 1H,ArH) 7.29-7.37 (m, 3H, ArH) 7.42-7.47 (m, 3H, ArH) 7.54-7.59 (m, 1H,ArH) 7.77-7.82 (m, 2H, ArH) 7.98 (d, J=7.8 Hz, 1H, ArH).

<Example 121> Carbonic acid9b-acetylamino-7-isopropyl-10-oxo-9b,10-dihydro-5-oxa-indeno[2,1-a]inden-4b-ylester phenyl ester

Phenyl chloroformate (0.35 g, 2.22 mmol, and trimethylamine (0.18 g,1.77 mmol were added to a solution ofN-(4b-Hydroxy-7-isopropyl-10-oxo-4b,10-dihydro-5-oxa-indeno[2,1-a]inden-9b-yl)-acetamide(0.50 g, 1.48 mmol in anhydrous THF, and heated for 24 hrs under reflux.After removal of THF by vacuum concentration, the residue was diluted inethylacetate and washed many times with an aqueous sodium bicarbonatesolution. The organic layer was dried, filtered and purified by columnchromatography (ethylacetate:hexane=1:1) to afford the title compound.10 mg (1.5%).

¹H-NMR (300 MHz, CDCl₃) δ 1.17 (dd, J=3.9, 6.9 Hz, 6H, CH₃) 2.04 (s, 3H,CH₃) 2.78-2.87 (m, 1H, CH) 6.13 (s, 1H, NH) 6.71 (s, 1H, ArH) 6.90 (d,J=7.8 Hz, 1H, ArH) 7.16 (d, J=7.8 Hz, 2H, ArH) 7.36-7.46 (m, 4H, ArH)7.61 (t, J=7.8 Hz, 1H, ArH) 7.81 (t, J=7.5 Hz, 1H, ArH) 7.88 (d, J=7.5Hz, 1H, ArH) 8.07 (d, J=9.0 Hz, 1H, ArH).

<Example 122> Phenyl-thiocarbamic acidO-(9b-azido-7-isopropyl-10-oxo-9b,10-dihydro-5-oxa-indeno[2,1-a]inden-4b-yl)ester

Phenyl isothiocyanate (0.62 g, 4.66 mmol) and trimethylamine (0.37 g,3.73 mmol) were added to a solution of9b-azido-4b-hydroxy-7-isopropyl-4b,9b-dihydro-5-oxa-indeno[2,1-a]inden-10-one(1.00 g, 3.11 mmol) in anhydrous THF, and heated for 24 hrs underreflux. After removal of THF by vacuum concentration, the residue wasdiluted in ethylacetate and washed many times with an aqueous sodiumbicarbonate solution. The organic layer was dried, filtered and purifiedby column chromatography (ethylacetate:hexane=1:2) to afford the titlecompound. 0.15 g (10%).

¹H-NMR (300 MHz, CDCl₃) δ 1.23 (d, J=6.9 Hz, 6H, CH₃) 2.86-2.95 (sept,1H, CH) 6.84 (s, 1H, NH) 6.95-7.05 (m, 3H, ArH) 7.29 (d, J=7.5 Hz, 1H,ArH) 7.36 (d, J=8.1 Hz, 2H, ArH) 7.46-7.61 (m, 3H, ArH) 7.71 (t, J=7.5Hz, 1H, ArH) 7.91 (d, J=7.8 Hz, 1H, ArH).

<Example 123>9b-Acetamido-1-amino-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-4b-ylethyl carbonate

Iron powder (0.45 g, 8.0 mmol) and conc. HCl (0.03 ml) were added to asolution of9b-acetamido-7-isopropyl-1-nitro-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-4b-ylethyl carbonate (0.50 g, 1.1 mmol) in ethanol (10 ml) and water (1 ml),and heated for 1 hr under reflux. The reaction mixture was washed withMeOH, filtered, and concentrated in a vacuum. Purification thoroughcolumn chromatography (ethylacetate:hexane=1:2) afforded the titlecompound. 0.32 g (69%).

¹H-NMR (300 MHz, CDCl₃) δ 1.16-1.19 (m, 9H, CH₃) 2.17 (s, 3H, CH₃)2.80-2.89 (m, 1H, CH) 4.05-4.15 (m, 2H, OCH₂) 4.44 (s, 3H, NCH₂) 5.33(s, 1H, NH) 6.72 (s, 1H, ArH) 6.90 (d, J=7.8 Hz, 1H, ArH) 6.96 (d, J=7.8Hz, 1H, ArH) 7.23-7.25 (m, 1H, ArH) 7.32 (t, J=7.8 Hz, 1H, ArH) 7.41 (d,J=7.8 Hz, 1H, ArH).

<Example 124>N,N′-(7-Isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofurane-4b,9b-diyldipropionamide

To 4b,9b-diamino-7-isopropyl-4bH-benzo[d]indeno[1,2-b]furan-10(9bH)-one(0.50 g, 1.70 mmol was added 10 ml of THF. This solution was stirredovernight, together with Et₃N (0.94 ml, 6.79 mmol and propionyl chloride(0.44 ml, 5.09 mmol, at room temperature. After vacuum concentration,purification by column chromatography (ethylacetate:hexane=2:1) affordedthe title compound (0.27 g, 39%).

¹H-NMR (300 MHz, CDCl₃) δ 1.05-1.17 (m, 12H), 2.08-2.39 (m, 4H), 2.82(q, J=7.6 Hz, 1H), 6.27 (s, 1H), 6.51 (s, 1H), 6.67 (s, 1H), 6.85 (d,J=7.8 Hz, 1H), 7.39 (d, J=8.4 Hz, 1H), 7.56 (t, J=8.4 Hz, 1H), 7.75 (t,J=8.4 Hz, 1H), 7.85 (d, J=7.8 Hz, 2H).

<Example 125>N,N′-(7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofurane-4b,9b-diylbis(2-methylpropanamide)

To 4b,9b-diamino-7-isopropyl-4bH-benzo[d]indeno[1,2-b]furan-10(9bH)-one(0.50 g, 1.70 mmol was added 10 ml of THF. This solution was stirredovernight, together with Et₃N (0.94 ml, 6.79 mmol and isobutyrylchloride (0.53 ml, 5.09 mmol, at room temperature. After vacuumconcentration, purification by column chromatography(ethylacetate:hexane=1:1) afforded the title compound. 0.27 g (39%).

¹H-NMR (300 MHz, CDCl₃) δ 1.05-1.20 (m, 18H), 2.35-2.46 (m, 2H), 2.80(q, J=6.9 Hz, 1H), 6.43 (s, 1H), 6.65 (s, 1H), 6.78 (s, 1H), 6.83 (d,J=7.5 Hz, 1H), 7.36 (d, J=8.0 Hz, 1H), 7.52 (t, J=8.0 Hz, 1H), 7.71 (t,J=8.5 Hz, 1H), 7.82 (t, J=8.5 Hz, 2H).

<Example 126>4b,9b-Dihydroxy-7-isopropyl-4bH-benzofuro[2′,3′:3,4]cyclopenta[1,2-b]pyridin-10(9bH)-one

To 5H-cyclopenta[b]pyridin-7(6H)-one (1.50 g, 11.26 mmol were added 10ml of dioxane and 1 ml of AcOH. The solution was stirred overnight,together with SeO₂ (3.75 g, 33.79 mmol, in a refluxer. Neutralizationwith a NaHCO₃ solution was followed by extraction with ethylacetate. Theextract was concentrated in a vacuum to give6,6-dihydroxy-5H-cyclopenta[b]pyridine-5,7(6H)-dione (1.50 g, 8.37mmol). This was dissolved in 10 ml of AcOH and stirred overnight,together with isopropylphenol (1.14 g, 8.37 mmol, in a refluxer.Concentration in a vacuum and purification by column chromatography(ethylacetate:hexane=2:1) afforded the title compound (0.70 g, 21%).

¹H-NMR (300 MHz, CDCl₃) δ 1.17 (d, J=4.1 Hz, 3H), 1.19 (d, J=4.1 Hz,3H), 2.85 (q, J=7.2 Hz, 1H), 3.77 (s, 1H), 6.74 (s, 1H), 6.94 (d, J=7.5Hz, 1H), 7.27 (d, J=5.2 Hz, 1H), 7.58 (d, J=7.5 Hz, 1H), 7.65 (s, 1H),8.07 (d, J=7.9 Hz, 1H).

<Example 127>10-Hydroxy-7-isopropyl-9b,10-dihydro-4bH-indeno[1,2-b]benzofurane-4b,9b-diyldiacetate

A solution of7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofurane-4b,9b-diyldiacetate (0.10 g, 0.26 mmoles) in absolute MeOH (5 mL) was stirred,together with sodium borohydride (20 mg, 0.53 mmoles), at roomtemperature for 7 hrs. Acetone (5 mL) was added, and the reactionmixture was stirred for 10 min until reaction stopped. Then, the solventwas removed. The reaction mixture was extracted with DCM and water,dried, concentrated in a vacuum, and purified by silica gel columnchromatography (30% ethylacetate mixed with 20% hexane) to afford thetitle compound. 30 mg (30%).

¹H-NMR (300 MHz, CDCl₃) δ 1.15 (dd, J=3.6 Hz, J=6.9 Hz, 6H, CH₃) 2.10(s, 3H, OAc) 2.16 (s, 3H, OAc) 2.81 (septet, J=6.9 Hz, 1H, CH) 4.38 (d,J=3 Hz, 1H, OH) 5.93 (d, J=3 Hz, 1H, CH) 6.72 (s, 1H, ArH) 6.81 (d,J=8.1 Hz, 1H, ArH) 7.36-7.50 (m, 3H, ArH) 7.57 (d, J=7.8 Hz, 1H, ArH).

<Example 128>9b-Hydroxy-7-isopropyl-4b-(methoxyamino)-4bH-indeno[1,2-b]benzofuran-10(9bH)-oneO-methyl oxime

O-methyl hydroxylamine hydrochloride (564 mg, 6.75 mmoles) was added toa solution of4b,9b-dihydroxy-7-isopropyl-4bH-indeno[1,2-b]benzofuran-10(9bH)-one(1.00 g, 3.37 mmoels) in hydrous pyridine (10 ml) and stirred at roomtemperature. After 3 hrs, the solvent was removed and the reactionmixture was washed with DCM and 1N HCl. The organic layer was washedagain with water and brine, concentrated in a vacuum, and separated bysilica gel column chromatography (30% ethylacetate mixed with 10%hexane) to afford the title compound. 100 mg (9%).

¹H-NMR (300 MHz, CDCl₃) δ 1.20 (d, J=6.9 Hz, 6H, CH₃) 2.81 (septet,J=6.9 Hz 1H, CH) 3.98 (s, 3H, N—OCH₃), 4.09 (s, 3H, N—OCH₃), 4.46 (s,1H, OH) 6.57 (dd, J=1.8 Hz, J=8.1 Hz, 1H, ArH) 6.82 (d, J=8.1 Hz, 1H,ArH) 6.88 (d, J=1.5 Hz, 1H, ArH) 7.44-7.55 (m, 2H, ArH) 7.87 (dd, J=1.2Hz, 6.9 Hz, 1H, ArH) 8.20 (dd, J=1.2 Hz, J=6.9 Hz, 1H, ArH) 8.73 (s, 1H,NH).

<Example 129>7-Isopropyl-4b-methoxy-10-methylene-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-ol

A dilution of 1 M potassium tertiary butoxide (1.25 mL, 1.25 mmol) inTHF was slowly added at 0° C. to a solution of methyltriphenylphosphonium bromide (415 mg, 1.16 mmol) in anhydrous THF (5mL), and stirred at 0° C. for 30 min and then at room temperature for 3hrs. To this, a solution of9b-hydroxy-7-isopropyl-4b-methoxy-4bH-benzo[d]indeno[1,2-b]furan-10(9bH)-one(0.30 g, 0.97 mmoles) in anhydrous THF (5 mL) was slowly added at 0° C.,and heated for 24 hrs under reflux. The reaction mixture wasconcentrated in a vacuum, and washed with water (50 mL) and DCM (50mL×2). The organic layer was washed again with water (30 mL) and brine(30 mL), dried over sodium sulfate, filtered, and concentrated in avacuum. Purification by column chromatography (30% ethylacetate mixedwith 10% hexane) afforded the title compound. 30 mg (10%).

¹H-NMR (300 MHz, CDCl₃) δ 1.16 (dd, J=3 Hz, J=6.9 Hz, 6H, CH₃) 2.81(sept, J=6.9 Hz, 1H, CH) 2.97 (br, 1H, OH) 3.67 (s, 3H, OMe) 5.71 (d,J=9.9 Hz, 2H, olefinic CH₂) 6.69 (s, 1H, ArH) 6.80 (dd, J=1.2 Hz, J=7.8Hz, 1H, ArH) 7.35-7.40 (m, 3H, ArH) 7.46-7.51 (m, 1H, ArH) 7.66-7.68 (m,1H, ArH).

<Example 130>9b-Hydroxy-7-isopropyl-4b-methoxy-4bH-indeno[1,2-b]benzofuran-10(9bH)-oneO-methyl oxime

O-methyl hydroxylamine hydrochloride (269 mg, 3.20 mmoles) was added toa solution of9b-hydroxy-7-isopropyl-4b-methoxy-4bH-indeno[1,2-b]benzofuran-10(9bH)-one(0.50 g, 1.61 mmoels) in anhydrous pyridine (10 ml) and stirredovernight at room temperature. After removal of the solvent, the residuewas washed with DCM and 1N HCl. The organic layer was washed again withwater and brine, concentrated in a vacuum, and purified by silica gelcolumn chromatography (30% ethylacetate mixed with 20% hexane) to affordthe title compound. 60 mg (11%).

¹H-NMR (300 MHz, CDCl₃) δ 1.20 (dd, J=2.4 Hz, J=6.9 Hz, 6H, CH₃) 1.40(s, 3H, CH₃), 1.46 (s, 3H, CH₃), 2.87 (septet, 1H, CH) 6.76 (d, J=0.9Hz, 1H, ArH) 6.92 (dd, J=1.2 Hz, J=7.8 Hz, 1H, ArH) 7.55-7.60 (m, 2H,ArH) 7.77-7.82 (m, 2H, ArH) 7.90 (m, 1H, ArH).

<Example 131> Mixture of 1-bromo and4-bromo-4b,9b-dihydroxy-7-isopropyl-4bH-indeno[1,2-b]benzofuran-10(9bH)-one

To a solution of 4-bromo-1-indanone (10.0 g, 47.4 mmol) in AcOH (4.0 mL)and dioxane (40 mL) was added SeO₂ (11.5 g, 104 mmol), followed byheating for 4 hrs under reflux. The reaction mixture was filtered andconcentrated to give a dark brown oil. m-Isopropylphenol (6.81 g, 50.0mmol) and AcOH (10 mL) were added to the dark brown oil and stirredovernight. The reaction mixture was purified by column chromatography(eluted with EtOAc/hexane=1/4-1/2) to afford the title compound as abrown solid. 9.28 g (52%).

¹H-NMR (300 MHz, CDCl₃) δ 1.17 (d, J=6.9 Hz, 6H), 2.84 (heptet, J=6.9Hz, 1H), 4.07 (s, br, 1H), 4.81 (s, br, 1H), 6.71 (s, 0.34H), 6.79 (d,J=1.2 Hz, 0.66H), 6.85 (dd, J=7.9, 1.2 Hz, 1H), 7.37-7.42 (m, 1.64H),7.57-7.62 (m, 0.36H), 7.67-7.75 (m, 1H), 7.91-7.97 (m, 1H).

<Example 132>1-(Benzylamino)-4b,9b-dihydroxy-7-isopropyl-4bH-indeno[1,2-b]benzofuran-10(9bH)-one

Benzaldehyde (0.30 g, 2.88 mmol) and NaCNBH₃ (0.12 g, 1.92 mmol) wereadded at 0° C. to a solution of1-amino-4b,9b-dihydroxy-7-isopropyl-4b,9b-dihydro-5-oxa-indeno[2,1-a]inden-10-one(0.30 g, 0.96 mmol) in absolute MeOH (3 ml), followed by reactionovernight at room temperature. The solvent was removed by vacuumconcentration, and purification by column chromatography(ethylacetate:hexane=1:4) afforded the title compound. 80 mg (15%).

¹H-NMR (300 MHz, CDCl₃) δ 1.18 (d, J=6.9 Hz, 6H, CH₃) 2.79-2.88 (m, 1H,CH) 4.50 (d, J=6.0 Hz, 2H, CH₂) 6.57 (d, J=8.1 Hz, 1H, ArH) 6.73 (s, 1H,ArH) 6.83 (d, J=7.8 Hz, 1H, ArH) 7.11 (d, J=7.2 Hz, 1H, ArH) 7.31-7.39(m, 5H, ArH) 7.47-7.53 (m, 2H, ArH).

<Example 133>1-(Ethylamino)-4b,9b-dihydroxy-7-isopropyl-4bH-indeno[1,2-b]benzofuran-10(9bH)-one

Acetaldehyde (0.08 g, 1.92 mmol) and NaCNBH₃ (0.08 g, 1.28 mmol) wereadded at 0° C. to a solution of1-amino-4b,9b-dihydroxy-7-isopropyl-4b,9b-dihydro-5-oxa-indeno[2,1-a]inden-10-one(0.20 g, 0.64 mmol) in absolute MeOH (3 ml), and reacted at roomtemperature for 2 days. After removal of the solvent by vacuumconcentration, column chromatography (ethylacetate:hexane=1:2) wasperformed to afford the title compound. 40 mg (18%).

¹H-NMR (300 MHz, CDCl₃) δ 1.16 (d, J=6.6 Hz, 6H, CH₃) 1.26 (t, J=6.9 Hz,3H, CH₃) 2.77-2.88 (m, 1H, CH) 3.16-3.25 (m, 2H, CH₂) 6.57 (d, J=8.1 Hz,1H, ArH) 6.65 (s, 1H, NH) 6.80 (d, J=7.5 Hz, 1H, ArH) 6.94 (s, 1H, ArH)7.07 (d, J=7.2 Hz, 1H, ArH) 7.39 (d, J=7.2 Hz, 1H, ArH) 7.54 (t, J=8.1Hz, 1H, ArH).

<Example 134>9b-Hydroxy-7-isopropyl-4b-methyl-4bH-indeno[1,2-b]benzofuran-10(9bH)-one

7-Isopropyl-4b-methoxy-10-methylene-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-ol(50 mg, 0.16 mmoles) was dissolved in THF:conc HCl (1:1, 1 mL) andheated for 30 min under reflux. After removal of the solvent, theresidue was washed DCM (50 ml) and water (20 ml). The organic layer waswashed again with water and brine, and concentrated in a vacuum. Theconcentrate was purified by silica gel column chromatography (30%ethylacetate mixed with 15% hexane) to afford the title compound. 20 mg(40%)

¹H-NMR (300 MHz, CDCl₃) δ 1.16 (dd, J=2.7 Hz, J=6.9 Hz, 6H, CH₃) 1.79(s, 3H, CH₃) 2.82 (sept, J=6.9 Hz, 1H, CH) 3.29 (s, 1H, OH) 6.67 (d, J=1Hz, 1H, ArH) 6.80 (dd, J=1 Hz, J=7.8 Hz, 1H, ArH) 7.35 (d, J=7.8 Hz, 1H,ArH) 7.50 (t, J=7.8 Hz, 1H, ArH) 7.72-7.78 (m, 2H, ArH) 7.83 (d, J=7.8Hz, 1H, ArH).

<Example 135>4b,9b-Dihydroxy-5-isobutyryl-7,8-dimethyl-4b,5-dihydroindeno[1,2-b]indol-10(9bH)-one

Conc. HCl (5 ml) was added to a solution ofN-(2-(2-hydroxy-1,3-dioxo-2,3-dihydro-1H-inden-2-yl)-4,5-dimethylphenyl)isobutyramide(200 mg, 0.57 mmoles) in THF (5 ml) and stirred for 8 hrs. An excess ofwater (50 ml) was added to terminate the reaction, followed byextraction with ethylacetate and water. The organic layer was washedwith brine, concentrated and purified by silica gel columnchromatography (30% ethylacetate mixed with 20% hexane) to afford thetitle compound. 120 mg (6%).

¹H-NMR (300 MHz, CDCl₃) δ 1.20 (d, J=6.9 Hz, 3H, CH₃) 1.25 (d, J=6.9 Hz,3H, CH₃) 2.16 (s, 3H, CH₃) 2.17 (s, 3H, CH₃) 2.74 (sept, J=6.9 Hz, 1H,CH) 3.91 (s, 1H, OH) 4.90 (s, 1H, OH) 6.48 (s, 1H, ArH) 7.30 (s, 1H,ArH) 7.46-7.54 (m, 1H, ArH) 7.72-7.83 (m, 3H, ArH).

<Example 136>7-Isopropyl-10-methyl-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-4b,9b-diol

7-Isopropyl-10-methylene-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-4b,9b-diol(50 mg, 0.20 mmol) was dissolved in absolute MeOH (5 mL) and stirred for24 hrs in the presence of Pd/C (10%, 10 mg) in a hydrogen atmosphere.The reaction mixture was washed with DCM, filtered through a cellitefiler, and concentrated. Purification by silica gel columnchromatography (30% ethylacetate mixed with 20% hexane) afforded thetitle compound. 30 mg (60%)

¹H-NMR (300 MHz, CDCl₃) δ 1.13-1.19 (m, 6H+3H, CH₃) 2.73-2.83 (sept,J=6.9 Hz, 1H, CH) 3.66-3.74 (m, 1H, CH) 3.82 (s, 1H, OH) 6.34 (d, J=8.1Hz, 0.8H, ArH) 6.52 (dd, J=1.5 Hz, J=8.1 Hz, 0.8H, ArH) 6.78 (d, J=1.5Hz, 0.8H, ArH) 7.46-7.51 (m, 1.6H, ArH) 7.70-7.75 (m, 0.8H, ArH) 8.50(s, 1H, ArH).

<Example 137>N-(1-Bromo-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)acetamide

Oxalyl chloride (0.60 mL, 6.88 mmol) and DMF (3 drops) were added to asolution of1-bromo-4b,9b-dihydroxy-7-isopropyl-4bH-indeno[1,2-b]benzofuran-10(9bH)-one(1.98 g, 5.28 mmol) in DCM (20 mL), and stirred at room temperature for3 hrs. The reaction was terminated by addition of water, followed byextraction with DCM and water. The organic layer was dried andconcentrated in a vacuum to give1-bromo-9b-chloro-4b-hydroxy-7-isopropyl-4bH-indeno[1,2-b]benzofuran-10(9bH)-oneas a solid. 1.81 g.

To a solution of1-bromo-9b-chloro-4b-hydroxy-7-isopropyl-4bH-indeno[1,2-b]benzofuran-10(9bH)-one(1.81 g) in THF (15 mL) was added 2.0 M NH₃ in i-PrOH (8.0 mL, 16 mmol)at 0° C. After 30 min, the temperature was elevated to room temperature,and the solution was stirred for 1 hr. The reaction was terminated byaddition of water, followed by extraction with ethylacetate and water.The organic layer was dried and concentrated in a vacuum to obtain 1.57g of9b-amino-1-bromo-4b-hydroxy-7-isopropyl-4bH-indeno[1,2-b]benzofuran-10(9bH)-oneas a dark brown solid.

This compound (1.55 g) was dissolved in acetic acid (5 ml) and heatedfor 30 min in the presence of Ac₂O (390 mg, 3.82 mmol) under reflux. Thereaction mixture was extracted with ethylacetate and water, and theorganic layer was concentrated in a vacuum and purified by columnchromatography (eluted with EtOAc/hexane=1/1-1/1) to afford the titlecompound as a yellow solid. 510 mg (23%).

¹H-NMR (500 MHz, CDCl₃) (major:minor=58:42 regioisomeric mixture) δ1.16-1.18 (m, 6H), 2.06 (s, 1.7H from major), 2.08 (s, 1.3H from minor),2.81-2.85 (m, 1H), 6.44 (s, br, 0.58H), 6.70 (d, br, J=1.4 Hz, 0.84H),6.78 (d, J=1.4 Hz, 0.58H), 6.83-6.86 (m, 1H), 7.25 (d, J=8.1 Hz, 0.42H),7.29 (d, J=7.9 Hz, 0.58H), 7.40 (t, J=7.7 Hz, 0.58H), 7.61 (t, J=7.7 Hz,0.42H), 7.69 (dd, J=7.8, 0.9 Hz, 0.42H), 7.75 (dd, J=7.6, 0.8 Hz,0.58H), 7.91 (dd, J=7.8, 1.0 Hz, 0.58H), 7.95 (dd, J=7.7, 0.9 Hz,0.48H).

<Example 138>4b,9b-Dihydroxy-5-isobutyryl-7,8-dimethoxy-5,9b-dihydro-4bH-indeno[1,2-b]indol-10-one

Conc. HCl (5 ml) was added to a solution ofN-[2-(2-hydroxy-1,3-dioxo-indan-2-yl)-4,5-dimethoxy-phenyl]-isobutyramide(500 mg, 1.30 mmol) in anhydrous THF (5 ml), and stirred at roomtemperature for 3 hrs. The reaction mixture was washed many times withethylacetate and water, and the organic layer was dried, filtered, andconcentrated in a vacuum, followed by column chromatography(ethylacetate:hexane=1:4) to afford the title compound. 100 mg (20%).

¹H-NMR (300 MHz, CDCl₃) δ 1.19-1.37 (m, 6H, CH₃) 2.70-2.80 (m, 1H, CH),3.10 (s, 1H, CH) 3.78 (s, 3H, OMe) 3.84 (s, 3H, OMe) 4.87 (s, 1H, OH)6.25 (s, 1H, ArH), 6.97 (s, 1H, ArH), 7.51 (t, J=7.2 Hz, 1H, ArH)7.73-7.82 (m, 3H, ArH).

<Example 139>4b,9b-Dihydroxy-7-isopropyl-2-piperidinyl-4bH-benzo[d]indeno[1,2-b]furan-10(9bH)-one

Piperidine (136 mg, 1.60 mmol), and triethylamine (200 mg, 1.98 mmol)were added to a solution of4b,9b-dihydroxy-7-isopropyl-2-fluoro-4bH-benzo[d]indeno[1,2-b]furan-10(9bH)-one(250 mg, 0.80 mmol) in N,N-dimethylformamide (2 ml) and reacted at 110°C. for 10 min by microwaving. The product was purified by columnchromatography to afford the title compound as a yellow solid (50 mg,8%).

¹H-NMR (300 MHz, CD₃OD) δ 1.18 (d, J=6.9 Hz, 6H), 1.68 (s, 8H), 2.82(sep, J=6.9H, 1H), 3.49 (s, 4H), 6.66 (s, 1H), 6.81 (d, J=7.6 Hz, 1H),7.07 (d, J=9 Hz, 1H), 7.22 (d, J=1.2 Hz, 1H), 7.41 (d, J=7.7 Hz, 1H),7.55 (d, J=8.6 Hz, 1H).

<Example 140>4b,9b-Dihydroxy-7-isopropyl-2-morpholinyl-4bH-benzo[d]indeno[1,2-b]furan-10(9bH)-one

Morpholine (140 mg, 1.60 mmol), and triethylamine (200 mg, 1.98 mmol)were added to a solution of4b,9b-dihydroxy-7-isopropyl-2-fluoro-4bH-benzo[d]indeno[1,2-b]furan-10(9bH)-one(250 mg, 0.80 mmol) in N,N-dimethylformamide (2 ml) and reacted at 110°C. for 10 min by microwaving. The product was purified by columnchromatography to afford the title compound as a yellow solid (60 mg,10%).

¹H-NMR (500 MHz, CD₃OD) δ 1.15 (t, J=5.8 Hz, 6H), 2.80 (sep, J=6.9H,1H), 3.32 (t, J=1.5 Hz, 4H), 3.76 (t, J=4.5 Hz, 4H), 6.68 (s, 1H), 6.81(d, J=7.6 Hz, 1H), 7.06 (d, J=8.3 Hz, 1H), 7.24 (s, 1H), 7.41 (d, J=7.8Hz, 1H), 7.57 (d, J=8.8 Hz, 1H).

<Example 141>4b,9b-Dihydroxy-7-isopropyl-1-piperidinyl-4bH-benzo[d]indeno-[1,2-b]furan-10(9bH)-one

Piperidine (140 mg, 1.60 mmol), and triethylamine (200 mg, 1.98 mmol)were added to a solution of4b,9b-dihydroxy-7-isopropyl-1-fluoro-4bH-benzo[d]indeno[1,2-b]furan-10(9bH)-one(250 mg, 0.80 mmol) in N,N-dimethylformamide (1 ml) and reacted 110° C.for 10 min by microwaving. The product was purified by columnchromatography to afford the title compound as a fluorescent yellowsolid (110 mg, 18%).

¹H-NMR (500 MHz, CD₃OD) δ 1.16 (dd, J=6.9 Hz, 4.9 Hz, 6H), 1.59 (quin,J=5.8 Hz, 2H), 1.74 (m, 4H), 2.81 (sep, J=6.9H, 1H), 3.02 (m, 2H), 3.09(m, 2H), 6.64 (s, 1H), 6.81 (d, J=7.8 Hz, 1H), 6.93 (d, J=8.2 Hz, 1H),7.35 (d, J=7.5 Hz, 1H), 7.38 (d, J=7.8 Hz, 1H), 7.61 (t, J=7.8 Hz, 1H).

<Example 142>4b,9b-Dihydroxy-7-isopropyl-1-morpholinyl-4bH-benzo[d]indeno[1,2-b]furan-10(9bH)-one

Morpholine (140 mg, 1.60 mmol), and triethylamine (200 mg, 1.98 mmol)were added to a solution of4b,9b-dihydroxy-7-isopropyl-1-fluoro-4bH-benzo[d]indeno[1,2-b]furan-10(9bH)-one(250 mg, 0.80 mmol) in N,N-dimethylformamide (1 ml) and reacted 110° C.for 10 min by microwaving. The product was purified by columnchromatography to afford the title compound as a fluorescent yellowsolid (80 mg, 13%).

¹H-NMR (500 MHz, CD₃OD) δ 1.14 (t, J=6.25 Hz, 6H), 2.79 (sep, J=6.8H,1H), 3.00 (m, 2H), 3.11 (m, 2H), 3.83 (s, 4H), 6.67 (s, 1H), 6.81 (d,J=8.0 Hz, 1H), 6.84 (d, J=8.2 Hz, 1H), 7.40 (d, J=7.8 Hz, 1H), 7.44 (d,J=7.5 Hz, 1H), 7.61 (t, J=7.8 Hz, 1H).

<Example 143>N-(1-Amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)propionamide

Trimethyl acetic anhydride (0.27 g, 1.46 mmol) was added to a solutionof 9b-chloro-4b-hydroxy-5,9b-dihydro-4bH-indeno[1,2-b]indol-10-one (0.50g, 1.46 mmol) in pivalic acid (5 ml), and heated at 100° C. for 30 min.The reaction mixture was diluted in ethylacetate, and washed many timeswith aq. NaHCO₃. The organic layer was dried, filtered, concentrated ina vacuum, and purified by column chromatography(ethylacetate:hexane=1:4) to afford the title compound. 50 mg (14%).

¹H-NMR (300 MHz, CDCl₃) δ 1.07 (t, J=7.5 Hz, 3H, CH₃) 1.16 (d, J=6.9 Hz,6H, CH₃) 2.24-2.32 (m, 2H, CH₂) 2.77-2.86 (m, 1H, CH) 6.64-6.65 (m, 2H,ArH) 6.82 (d, J=6.6 Hz, 1H, ArH) 6.98 (d, J=7.2 Hz, 1H, ArH) 7.33 (m,1H, ArH) 7.38-7.43 (m, 1H, ArH).

<Example 144>N-(1-Amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)butyramide

H₂O (0.5 ml), Fe (0.28 g, 5.14 mmol), and conc. HCl (0.03 mmol) wereadded to a solution ofN-(4b-hydroxy-7-isopropyl-1-nitro-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)butyramide(0.30 g, 0.70 mmol) in EtOH (5 ml) and heated for 1 hr under reflux. Thereaction mixture was washed with ethylacetate, and filtered. Then, thefiltrate was concentrated and purified by column chromatography(ethylacetate:hexane=1:4) to afford the title compound. 0.20 g (75%).

¹H-NMR (300 MHz, CD₃OD) δ 0.95 (t, J=7.5 Hz, 3H, CH₃) 1.16 (d, J=6.9 Hz,6H, CH₃) 1.56-1.63 (m, 1H, CH₂) 2.23 (t, J=7.5 Hz, 2H, CH₂) 2.79-2.83(m, 1H, CH) 6.64 (s, 2H, ArH) 6.82 (d, J=7.8 Hz, 1H, ArH) 6.98 (d, J=6.6Hz, 1H, ArH) 7.33 (s, 1H, ArH) 7.40 (t, J=6.6 Hz, 1H, ArH).

<Example 145>4b,9b-Dihydroxy-5-isobutyryl-7-isopropyl-5,9b-dihydro-4bH-indeno[1,2-b]indol-10-one

Conc. HCl (2 ml) was added to a solution ofN-[2-(2-hydroxy-1,3-dioxo-indan-2-yl)-5-isopropyl-phenyl]-isobutyramide(80 mg, 0.21 mmol) in anhydrous THF (2 ml) and stirred at roomtemperature for 3 hrs. The reaction mixture was washed many times withethylacetate and water, and the organic layer was dried, filtered, andconcentrated in a vacuum, followed by purification through columnchromatography (ethylacetate:hexane=1:4) to afford the title compound.33 mg (41%).

¹H-NMR (300 MHz, CDCl₃) δ 1.15-1.25 (m, 12H, CH₃) 2.68-2.84 (m, 2H, CH)3.08 (s, 1H, OH) 5.02 (s, 1H, OH) 6.51 (s, 1H, ArH) 6.76 (d, J=8.1 Hz,1H, ArH) 7.44 (d, J=8.1 Hz, 1H, ArH) 7.51 (t, J=7.5 Hz, 1H, ArH)7.73-7.84 (m, 3H, ArH).

<Example 146>4b,9b-Dihydroxy-7-isopropyl-2-(hydroxypiperidinyl)-4bH-benzo[d]indeno[1,2-b]furan-10(9bH)-one

Hydroxypiperidine (162 mg, 1.60 mmol), and triethylamine (200 mg, 1.98mmol) were added to a solution of4b,9b-dihydroxy-7-isopropyl-2-fluoro-4bH-benzo[d]indeno[1,2-b]furan-10(9bH)-one(250 mg, 0.80 mmol) in N,N-dimethylformamide (1 ml) and reacted at 110°C. for 5 min by microwaving. The product was purified by columnchromatography to afford the title compound as a yellow solid (65 mg,10%).

¹H-NMR (300 MHz, CD₃OD) δ 1.16 (dd, J=6.9 Hz, 1.4 Hz, 6H), 1.57 (m, 2H),1.95 (m, 2H), 2.80 (sep, J=6.9 Hz, 1H), 3.24 (m, 2H), 3.92 (m, 3H), 6.63(s, 1H), 6.80 (d, J=7.7 Hz, 1H), 7.12 (d, J=7.7 Hz, 1H), 7.25 (s, 1H),7.39 (d, J=7.6 Hz, 1H), 7.56 (d, J=8.0 Hz, 1H).

<Example 147>4b,9b-Dihydroxy-1-(4-hydroxypiperidin-1-yl)-7-isopropyl-4bH-benzo[d]indeno[1,2-b]furan-10(9bH)-one

Hydroxypiperidine (162 mg, 1.60 mmol) and triethylamine (200 mg, 1.98mmol) were added to a solution of4b,9b-dihydroxy-7-isopropyl-1-fluoro-4bH-benzo[d]indeno[1,2-b]furan-10(9bH)-one(250 mg, 0.80 mmol) in N,N-dimethylformamide (1 ml) and reacted 110° C.for 5 min by microwaving. The product was purified by columnchromatography to afford the title compound as a fluorescent yellowsolid (60 mg, 10%).

¹H-NMR (300 MHz, CD₃OD) δ 1.16 (d, J=6.6 Hz, 6H), 1.74 (m, 2H), 1.94 (s,2H), 2.79 (m, 3H), 3.44 (s, 1H), 3.76 (m, 1H), 6.63 (s, 1H), 6.81 (d,J=7.9 Hz, 1H,) 6.98 (d, J=7.9 Hz, 1H), 7.36 (d, J=7.5 Hz 2H), 7.63 (t,J=7.4 Hz, 1H).

<Example 148>4b,9b-Dihydroxy-7-isopropyl-2-(4-(4-methoxybenzyl)piperazin-1-yl)-4bH-benzo[d]indeno[1,2-b]furan-10(9bH)-one

1-(4-Methoxybenzyl)piperazine (136 mg, 1.60 mmol) and triethylamine (200mg, 1.98 mmol) were added to a solution of4b,9b-dihydroxy-7-isopropyl-2-fluoro-4bH-benzo[d]indeno[1,2-b]furan-10(9bH)-one(250 mg, 0.80 mmol) in N,N-dimethylformamide (1 ml) and reacted 110° C.for 5 min by microwaving. The product was purified by columnchromatography to afford the title compound as a yellow solid (70 mg,9%).

¹H-NMR (300 MHz, CD₃OD) δ 1.17 (d, 6.8 Hz), 2.60 (s, 4H), 2.80 (sep,J=6.8 Hz, 1H), 3.47 (s, 4H), 3.55 (s, 2H), 3.80 (s, 3H), 6.74 (s, 1H),6.78 (Br, 1H), 6.87 (d, J=7.8 Hz, 2H), 6.93 (s, 1H), 7.23 (m, 3H), 7.40(br, 1H), 7.60 (br, 1H).

<Example 149>4b,9b-Dihydroxy-7-isopropyl-1-(4-(4-methoxybenzyl)piperazin-1-yl)-4bH-benzo[d]indeno[1,2-b]furan-10(9bH)-one

1-(4-methoxybenzyl)piperazine (140 mg, 1.60 mmol) and triethylamine (200mg, 1.98 mmol) were added to a solution of4b,9b-dihydroxy-7-isopropyl-1-fluoro-4bH-benzo[d]indeno[1,2-b]furan-10(9bH)-one(250 mg, 0.80 mmol) in N,N-dimethylformamide (1 ml), and reacted 110° C.for 5 min by microwaving. The product was purified by columnchromatography to afford the title compound as a fluorescent yellowsolid (84 mg, 11%).

¹H-NMR (300 MHz, CD₃OD) δ1.16 (d, J=6.9 Hz, 6H), 2.65 (m, 4H), 2.81(sep, J=6.9 Hz, 1H), 3.18 (t, J=4.6 Hz, 4H), 3.53 (d, 2.6 Hz, 2H), 3.80(s, 3H), 6.70 (s, 1H), 6.79 (d, J=7.8 Hz, 1H), 6.89 (m, 3H), 7.43 (d,J=7.4 Hz, 1H), 7.62 (t, J=7.8 Hz).

<Example 150>2-(Dimethylamino)-4b,9b-dihydroxy-7-isopropyl-4bH-benzo[d]indeno[1,2-b]-furan-10(9bH)-one

Dimethylamine hydrochloride (136 mg, 1.60 mmol) and triethylamine (400mg, 3.96 mmol) were added to a solution of4b,9b-dihydroxy-7-isopropyl-2-fluoro-4bH-benzo[d]indeno[1,2-b]furan-10(9bH)-one(250 mg, 0.80 mmol) in N,N-dimethylformamide (1 ml) and reacted 110° C.for 5 min by microwaving. The product was purified by columnchromatography to afford the title compound as a yellow solid (73 mg,10%).

¹H-NMR (300 MHz, CD₃OD) δ 1.16 (d, J=6.9 Hz, 6H), 2.82 (sep, J=6.9 Hz,1H), 3.14 (s, 6H), 6.71 (s, 1H), 6.80 (t, J=7.5 Hz, 2H), 7.05 (d, J=7.8Hz, 1H), 7.43 (d, J=7.8 Hz, 1H), 7.62 (d, J=8.8 Hz, 1H).

<Example 151>1-(Dimethylamino)-4b,9b-dihydroxy-7-isopropyl-4bH-benzo[d]indeno[1,2-b]-furan-10(9bH)-one

Dimethylamine hydrochloride (140 mg, 1.60 mmol) and triethylamine (400mg, 3.96 mmol) were added to a solution of4b,9b-dihydroxy-7-isopropyl-1-fluoro-4bH-benzo[d]indeno[1,2-b]furan-10(9bH)-one(250 mg, 0.80 mmol) in N, N-dimethylformamide (1 ml) and reacted 110° C.for 10 min by microwaving. The product was purified by columnchromatography to afford the title compound as a yellow solid (168 mg,31%).

¹H-NMR (300 MHz, CD₃OD) δ1.17 (dd, J=6.9, 2.8 Hz, 6H), 2.82 (sep, J=6.9Hz, 1H), 2.95 (s, 6H), 6.71 (d, J=1.25 Hz, 1H), 6.80 (m, 2H), 7.30 (t,J=7.9 Hz, 2H), 7.57 (t, J=7.4 Hz, 1H).

<Example 152>10-Hydrazono-7-isopropyl-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-4b,9b-diol

4b,9b-dihydroxy-7-isopropyl-4bH-benzo[d]indeno[1,2-b]furan-10(9bH)-one(500 mg, 1.69 mmol) and hydrazine monohydrate (125 mg, 2.50 mmol) weredissolved in toluene (5 ml) in a reactor, and stirred overnight at roomtemperature. The product was purified by column chromatography to affordthe title compound as a white solid (7 mg, 1%).

¹H-NMR (300 MHz, DMSO) δ 1.15 (d, J=6.9 Hz, 6H), 2.80 (sep, J=6.8 Hz,1H), 5.83 (br, 1H), 6.72˜6.76 (m, 2H), 7.48 (t, J=7.8 Hz, 1H), 7.64˜7.70(m, 2H), 7.75 (d, J=7.9 Hz, 1H), 7.83 (d, J=7.7 Hz, 1H), 11.24 (s, 1H).

<Example 153>N-(1-Amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)benzamide

Iron powder (38 mg, 0.68 mmoles) was added to a solution ofN-(4b-hydroxy-7-isopropyl-1-nitro-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)benzamide(0.10 g, 0.23 mmoles) in ethanol:water (10:1, 10 mL) and heated for 3hrs under reflux. The reaction mixture was filtered, and the filtratewas concentrated in a vacuum and purified by silica gel columnchromatography (50% ethylacetate in hexane) to afford the titlecompound. 80 mg (86%).

¹H-NMR (300 MHz, CD₃OD) δ 1.18 (d, J=6.9 Hz, 6H, CH₃) 2.84 (sept, J=6.9Hz, 1H, CH) 6.67 (br, 2H, ArH) 6.87-6.89 (m, 1H, ArH) 7.01-7.03 (m, 1H,ArH) 7.40-7.54 (m, 5H, ArH) 7.83-7.86 (m, 2H, ArH).

<Example 154>N-(1-Amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-3-methoxybenzamide

N-(4b-hydroxy-7-isopropyl-1-nitro-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl-3-methoxybenzamide(0.10 g, 0.21 mmoles) was dissolved in ethanol:water (10:1, 10 mL) andheated for 3 hrs in the presence of iron powder (36 mg, 0.63 mmoles)under reflux. The reaction mixture was filtered, and the filtrate wasconcentrated in a vacuum and purified by silica gel columnchromatography (50% ethylacetate in hexane) to afford the titlecompound. 85 mg (90%).

¹H-NMR (300 MHz, CD₃OD) δ 1.19 (d, J=6.9 Hz, 6H, CH₃) 2.84 (sept, J=6.9Hz, 1H, CH) 3.82 (s, 3H, OCH₃) 6.67-6.72 (m, 2H, ArH) 6.89 (d, J=6.3 Hz,1H, ArH) 7.03-7.09 (m, 2H, ArH) 7.31-7.36 (m, 1H, ArH) 7.43-7.49 (m, 4H,ArH).

<Example 155>N-(1-Amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-4-chlorobenzamide

4-Chloro-N-(4b-hydroxy-7-isopropyl-1-nitro-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)benzamide(0.08 g, 0.17 mmoles) was dissolved in ethanol:water (10:1, 10 mL) andheated for 3 hrs in the presence of iron powder (28 mg, 0.50 mmoles)under reflux. The reaction mixture was filtered, and the filtrate wasconcentrated in a vacuum, and purified by silica gel columnchromatography (50% ethylacetate in hexane) to afford the titlecompound. 60 mg (80%).

¹H-NMR (300 MHz, CD₃OD) δ 1.18 (d, J=6.9 Hz, 6H, CH₃) 2.84 (sept, J=6.9Hz, 1H, CH) 6.66-6.75 (m, 2H, ArH) 6.88 (d, J=7.8 Hz, 1H, ArH) 7.01 (d,J=7.5 Hz, 1H, ArH) 7.41-7.46 (m, 4H, ArH) 8.83 (d, J=8.4 Hz, 2H, ArH).

<Example 156>N-(1-Amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-4-nitrobenzamide

N-(4b-hydroxy-7-isopropyl-1-nitro-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-4-nitrobenzamide(0.075 g, 0.15 mmoles) was dissolved in ethanol:water (10:1, 10 mL) andheated for 6 hrs in the presence of iron powder (52 mg, 0.92 mmoles)under reflux. The reaction mixture was filtered, and the filtrate wasconcentrated in a vacuum and purified by silica gel columnchromatography (50% ethylacetate in hexane) to afford the titlecompound. 50 mg (76%).

¹H-NMR (300 MHz, CD₃OD) δ 1.18 (d, J=6.9 Hz, 6H, CH₃) 2.83 (sept, J=6.9Hz, 1H, CH) 6.60-6.69 (m, 4H, ArH) 6.86-6.88 (m, 1H, ArH) 6.99-7.01 (m,1H, ArH) 7.40-7.46 (m, 2H, ArH) 7.60-7.63 (m, 2H, ArH).

<Example 157>1-Amino-4b,9b-dihydroxy-6,8-diisopropyl-4bH-benzo[d]indeno[1,2-b]furan-10(9bH)-one

4b,9b-Dihydroxy-6,8-diisopropyl-1-nitro-4bH-benzo[d]indeno[1,2-b]furan-10(9bH)-one(300 mg, 0.78 mmol) was dissolved in ethanol:water (10 ml:1 ml). To thissolution, Fe (319 mg, 5.7 mmol) and one drop of conc. HCl were added,followed by heating for 1 hr under reflux. After neutralization with aNaHCO₃ solution, concentration in a vacuum and purification by columnchromatography (20% methanol in methylene chloride) afforded the titlecompound (90 mg, 33%).

¹H-NMR (300 MHz, DMSO) δ 1.09˜1.17 (m, 12H), 2.81 (sep, J=6.8 Hz, 1H),2.93 (sep, J=6.8 Hz, 1H), 6.36 (s, 1H), 6.64˜6.68 (m, 2H), 6.97 (s, 1H),7.08 (d, J=1.2 Hz, 1H), 7.43 (t, J=7.7 Hz, 1H), 7.50 (s, 1H).

<Example 158>N-(1-Amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)cyclopropanecarboxamide

A solution ofN-(4b-hydroxy-7-isopropyl-1-nitro-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)cyclopropanecarboxamide(0.20 g, 0.49 mmoles) in ethanol:water (10:1, 20 mL) was heated for 3hrs in the presence of iron powder (82 mg, 1.47 mmoles) under reflux.The reaction mixture was filtered, and the filtrate was concentrated ina vacuum and purified by silica gel column chromatography (50%ethylacetate in hexane) to afford the title compound. 150 mg (81%).

¹H-NMR (300 MHz, CD₃OD) δ 0.74-0.76 (m, 4H, CH₂) 1.17 (d, J=6.9 Hz, 6H,CH₃) 1.72-1.75 (m, 1H, CH) 2.82 (sept, J=6.9 Hz, 1H, CH) 6.64 (m, 2H,ArH) 6.84-6.86 (m, 1H, ArH) 6.97-6.99 (m, 1H, ArH) 7.42 (m, 2H, ArH).

<Example 159>1-(4b-Hydroxy-6,8-diisopropyl-1-amino-10-oxo-9b,10-dihydro-4bH-benzo[d]-indeno[1,2-b]furan-9b-yl)-3-(4-methoxyphenyl)thiourea

1-(4b-hydroxy-6,8-diisopropyl-1-nitro-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)-3-(4-methoxyphenyl)thiourea(100 mg, 0.78 mmol) was dissolved in ethanol:water (10 ml:1 ml). To thissolution, Fe (319 mg, 5.7 mmol) and one drop of conc. HCl were added,and heated for 1 hr under reflux.

Concentration in a vacuum and purification by column chromatography (20%methanol in methylene chloride) afforded the title compound (60 mg,64%).

¹H-NMR (300 MHz, CD₃OD) δ 1.22 (d, J=6.9 Hz, 6H, CH₃), 2.84 (sep, J=6.9Hz, 1H, CH), 3.80 (s, 3H, OCH₃), 5.88 (d, J=7.3 Hz, 1H, ArH), 6.64˜6.67(m, 2H, ArH), 6.85˜6.89 (m, 3H, ArH), 6.98˜7.01 (m, 2H, ArH), 7.16 (t,J=7.8 Hz, 1H, ArH), 7.43 (d, J=8.0 Hz, 1H, ArH).

<Example 160>1-(4b-Hydroxy-6,8-diisopropyl-1-amino-10-oxo-9b,10-dihydro-4bH-benzo[d]-indeno[1,2-b]furan-9b-yl)-3-(phenyl)thiourea

1-(4b-hydroxy-6,8-diisopropyl-1-nitro-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)-3-(phenyl)thiourea(100 mg, 0.78 mmol) was dissolved in ethanol:water (10 ml:1 ml). To thissolution, Fe (319 mg, 5.7 mmol) and one drop of conc. HCl were added andheated for 1 hr under reflux. Concentration in a vacuum and purificationby column chromatography (20% methanol in methylene chloride) affordedthe title compound (40 mg, 43%).

¹H-NMR (300 MHz, acetone-d6) δ 1.21 (dd, J=6.9 Hz, 1.0 Hz, 6H, CH₃),2.84 (sep, J=6.9 Hz, 1H, CH), 5.79 (s, 1H, OH), 5.86 (d, J=7.3 Hz, 1H,ArH), 6.43 (s, 2H, NH₂), 6.71 (d, J=8.0 Hz, 1H, ArH), 6.74 (d, J=1.4 Hz,1H, ArH), 6.85 (dd, J=8.0 Hz, 1.4 Hz, 1H, ArH), 7.12˜7.22 (m, 3H, ArH),7.32˜7.35 (m, 3H, ArH), 7.45 (d, J=8.0 Hz, 1H, ArH), 8.73 (s, 1H, NH),8.78 (s, 1H, NH).

<Example 161>N-(4b-Hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)thiophene-2-carboxamide

Thiophene carboxylic acid (0.13 g, 1.01 mmol) was dissolved in anhydrousmethylene chloride (10 ml) and stirred overnight at 00° C. in thepresence of EDCl (0.19 g, 1.01 mmol), and HOBt (0.13 g, 1.01 mmol) (0.30g, 1.01 mmol). Since the reaction was not completed in spite of such along period of time, EDCl (0.19 g, 1.01 mmol) and HOBt (0.13 g, 1.01mmol) were further added. However, the completion of the reaction wasnot detected. The reaction mixture was diluted in methylene chloride,and washed with water. The organic layer was dried and filtered.Purification by column chromatography (ethylacetate:hexane=1:4) affordedthe title compound. 0.12 g (29%).

¹H-NMR (300 MHz, CDCl₃) δ 1.13-1.15 (m, 6H, CH₃) 2.76-2.85 (m, 1H, CH)6.71 (s, 1H, NH) 6.80 (d, J=7.8 Hz, 1H, ArH) 7.05 (s, 1H, ArH) 7.20 (s,1H, ArH) 7.33 (d, J=7.8 Hz, 1H, ArH) 7.50-7.55 (m, 2H, ArH) 7.61 (d,J=2.4 Hz, 1H, ArH) 7.76-7.87 (m, 2H, ArH) 8.01 (d, J=7.5 Hz, 1H, ArH).

<Example 162>1-(1-Amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-3-(4-methoxyphenylurea

1-(4b-hydroxy-7-isopropyl-1-nitro-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-3-(4-methoxyphenylurea(93 mg, 0.19 mmol was added to 5 ml of EtOH:H₂O (10:1) to form a paleyellowish turbid solution to which Fe powder (39 mg, 0.70 mmol and twodrops of conc. HCl were then added at room temperature, followed bystirring for 1.5 hrs under reflux. A new spot was observed just belowthe starting material, as monitored by TLC. The reaction mixture wasfiltered, concentrated, and purified by silica gel column chromatographyusing EtOAc/Hx (1/2-1/1) to afford the title compound as a pale yellowsolid (65 mg, 0.14 mmol, 74%).

¹H-NMR (300 MHz, CDCl₃+2 drops of CD₃OD) δ 1.18 (d, J=6.9 Hz, 6H), 2.38(s, br, 5H), 2.82 (heptet, J=6.9 Hz, 1H), 3.78 (s, 3H), 6.07 (d, J=7.4Hz, 1H), 6.58 (d, J=8.2 Hz, 1H), 6.68 (d, J=1.5 Hz, 1H), 6.81-6.87 (m,1H), 6.84 (d, J=9.0 Hz, 2H), 7.08 (d, J=9.0 Hz, 2H), 7.17 (t, J=7.8 Hz,1H), 7.34 (d, J=8.0 Hz, 1H).

<Example 163>1-(1-Amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-3-butylurea

1-Butyl-3-(4b-hydroxy-7-isopropyl-1-nitro-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)urea(100 mg, 0.228 mmol was added to 5 ml of EtOH:H₂O (10:1) to form a paleyellowish turbid solution to which Fe powder (38 mg, 0.680 mmol and twodrops of conc. HCl were then added at room temperature, followed bystirring for 2.5 hrs under reflux. A new spot was observed just belowthe starting material, as monitored by TLC. The reaction mixture wasfiltered, concentrated, and purified by silica gel column chromatographyusing EtOAc/Hx (1/2-1/1) to afford the title compound as a pale yellowsolid (66 mg, 0.16 mmol, 71%).

¹H-NMR (300 MHz, CDCl₃+a drop of CD₃OD) δ 0.87 (t, J=7.2 Hz, 3H), 1.16(dd, J=6.9, 0.8 Hz, 6H), 1.27 (sextet, J=7.4 Hz, 2H), 1.36-1.65 (m, 2H),2.10 (s, br, 3H), 2.79 (heptet, J=6.9 Hz, 1H), 3.16-3.28 (m, 1H),3.32-3.44 (m, 1H), 6.63 (d, J=8.2 Hz, 1H), 6.69 (d, J=1.5 Hz, 1H), 7.76(dd, J=8.1, 1.6 Hz, 1H), 6.93 (d, J=7.3 Hz, 1H), 7.15 (d, J=8.0 Hz, 1H),7.42 (dd, J=8.1, 7.4 Hz, 1H).

<Example 164>1-(1-Amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-3-(4-fluorophenyl)urea

1-(4-fluorophenyl)-3-(4b-hydroxy-7-isopropyl-1-nitro-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-ylurea(187 mg, 0.392 mmol was added to 5 ml of EtOH:H₂O (10:1) to form a paleyellowish turbid solution to which Fe powder (66 mg, 1.18 mmol and onedrop of conc. HCl were then added at room temperature, followed bystirring for 1 hr under reflux. A new spot was observed just below thestarting material, as monitored by TLC. The reaction mixture wasfiltered, concentrated, and purified by silica gel column chromatographyusing EtOAc/Hx (1/2-1/1) to afford the title compound as a pale yellowsolid (107 mg, 0.239 mmol, 61%).

¹H-NMR (300 MHz, CD₃OD) δ 1.23 (d, J=6.9 Hz, 6H), 2.85 (heptet, J=6.9Hz, 1H), 5.87 (d, J=7.3 Hz, 1H), 6.64-6.67 (m, 2H), 6.87 (dd, J=8.0, 1.6Hz, 1H), 7.05-7.20 (m, 5H), 7.48 (d, J=6.5 Hz, 1H).

<Example 165>1-(1-Amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-3-(tert-butylurea

1-(tert-Butyl-3-(4b-hydroxy-7-isopropyl-1-nitro-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-ylurea(99 mg, 0.23 mmol was added to 5 ml of EtOH:H₂O (10:1) to form a paleyellowish turbid solution to which Fe powder (38 mg, 0.688 mmol and twodrops of conc. HCl were then added at room temperature, followed bystirring for 1.5 hrs under reflux. A new spot was observed (PK344) justbelow the starting material, as monitored by TLC. The reaction mixturewas filtered, concentrated, and purified by silica gel columnchromatography using EtOAc/Hx (1/2-1/1) to afford the title compound asa yellow solid (84 mg, 0.21 mmol, 91%).

¹H-NMR (300 MHz, CD₃OD) δ 1.17 (dd, J=6.9, 1.9 Hz, 6H), 1.23 (s, 9H),2.73-2.88 (m, 1H), 6.58-6.72 (m, 2H), 6.81 (d, br, J=7.3 Hz, 1H), 6.99(d, br, J=6.9 Hz, 1H), 7.31 (d, br, J=7.2 Hz, 1H), 7.38-7.52 (m, 1H).

<Example 166>N-(1-Amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)formamide

N-(4b-hydroxy-7-isopropyl-1-nitro-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)acetamide(123 mg, 0.334 mmol was added to 5 ml of EtOH:H₂O (10:1) to form a paleyellowish turbid solution to which Fe powder (46 mg, 0.83 mmol) and onedrop of conc. HCl were then added at room temperature, followed bystirring for 2 hrs under reflux. A new spot was observed just below thestarting material, as monitored by TLC. The reaction mixture wasfiltered, concentrated, and purified by silica gel column chromatographyusing EtOAc/Hx (1/2-1/1) to afford the title compound as a yellow solid(72 mg, 0.21 mmol, 64%).

¹H-NMR (300 MHz, CD₃OD) δ 1.18 (dd, J=6.9, 1.4 Hz, 6H), 2.83 (heptet,J=6.9 Hz, 1H), 6.66 (s, 1H), 6.68-6.76 (m, 1H), 6.84 (d, J=7.9 Hz, 1H),7.00 (d, J=7.1 Hz, 1H), 7.33 (d, J=7.9 Hz, 1H), 7.41-7.50 (m, 1H), 8.10(s, 1H).

<Example 167>N-(1-Formamido-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]-indeno[1,2-b]furan-9b-yl)acetamide

A mixture of formic acid (5 ml) and acetic anhydride (10 ml) was stirredat 80° C. for 30 min and then cooled to room temperature. To thismixture was added a solution ofN-(1-amino-9b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-5-oxa-indeno[2,1-a]inden-4b-yl)-acetamide(200 mg, 0.57 mmol) in methylene chloride, followed by stirring at roomtemperature. After removal of the solvent, the addition of a smallamount of methylene chloride formed a white precipitate. This wasfiltered to afford the title compound (170 mg, 79%).

¹H-NMR (300 MHz, CD₃OD) δ 1.16 (dd, J=6.9 Hz, 1.6 Hz, 6H, CH₃), 1.99 (s,3H, CH₃), 2.82 (sep, J=6.9 Hz, 1H, CH), 6.65 (s, 1H, CH₃), 6.88 (dd,J=7.9 Hz, 1.0 Hz, 1H, ArH), 7.38 (d, J=7.9 Hz, 1H, ArH), 7.59 (d, J=7.6Hz, 1H, ArH), 7.75 (t, J=8.0 Hz, 1H, ArH), 8.46 (s, 1H), 8.50 (d, J=8.1Hz, 1H, ArH).

<Example 168>N-(1-Amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)methanesulfonamide

ToN-(4b-hydroxy-7-isopropyl-1-nitro-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)methanesulfonamide(150 mg, 0.36 mmol) were added a mixture of ethanol:water (10 ml:1 ml),Fe (80 mg, 1.43 mmol), and two drops of conc. HCl in that order. Afterheating for 2 hrs under reflux, the reaction mixture was concentrated ina vacuum and purified by column chromatography(ethylacetate:n-hexane=1:2) to afford the title compound (60 mg, 43%).

¹H-NMR (300 MHz, CD₃OD) δ 1.34 (d, J=6.9 Hz, 6H, CH₃), 3.09 (sep, J==6.9Hz, 1H, CH), 3.34 (s, 3H, SCH₃), 7.11 (d, J=7.7 Hz, 1H, ArH), 7.28˜7.35(m, 2H, ArH), 7.56 (s, 1H, ArH), 7.73 (d, J=7.9 Hz, 1H, ArH), 7.81 (d,J=8.1 Hz, 1H, ArH).

<Example 169> Diethyl(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)phosphoamidate

Diethyl(4b-hydroxy-7-isopropyl-4-nitro-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)phosphoamidate(0.050 g, 0.11 mmoles) was dissolved in a mixture of ethanol:water(10:1, 10 mL). To this solution, iron powder (20 mg, 0.36 mmoles) and2-3 drops of conc. HCl were added before heating for 2.5 hrs underreflux. After completion of the reaction, the reaction mixture waswashed with ethylacetate, filtered to remove iron powder, and extractedwith ethylacetate and water. The organic layer was washed with brine,dried, and concentration, followed by separation and purification bycolumn chromatography (30% ethylacetate mixed with 50% hexane) to affordthe title compound. 6 mg (13%).

¹H-NMR (300 MHz, CD₃OD) δ 1.13 (t, J=6.9 Hz, 6H, CH₃) 1.26 (d, J=6.9 Hz,6H, CH₃) 2.88 (sept, J=6.9 Hz, 1H, CH) 3.65-3.89 (m, 4H, CH₂) 6.69 (d,J=7.8 Hz, 1H, ArH) 6.83-6.86 (m, 2H, ArH) 7.03 (d, J=7.8 Hz, 1H, ArH)7.30 (d, J=8.1 Hz, 1H, ArH) 7.40 (t, J=8.1 Hz, 1H, ArH).

<Example 170>N-(1-Amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-4-cyanobenzamide

Iron powder (30 mg, 0.38 mmoles) and 3 drops of conc. HCl were added toa solution of4-cyano-N-(4b-hydroxy-7-isopropyl-4-nitro-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)benzamide(0.06 g, 0.13 mmoles) in ethanol:water (10:1, 20 mL), and heated for 3hrs under reflux. After completion of the reaction, the reaction mixturewas washed with ethylacetate, filtered to remove iron powder, andextracted with ethylacetate and water. The organic layer was washed withbrine, dried, and concentrated, followed by separation and purificationby column chromatography (30% ethylacetate mixed with 30% hexane) toafford the title compound. 50 mg (89%).

¹H-NMR (300 MHz, CD₃OD) δ 1.17 (d, J=6.9 Hz, 6H, CH₃) 2.83 (sept, J=6.9Hz, 1H, CH) 6.67 (br, 2H, ArH) 6.86-6.88 (m, 1H, ArH) 7.00-7.02 (m, 1H,ArH) 7.43-7.45 (m, 2H, ArH) 7.77-7.80 (m, 2H, ArH) 7.96-7.99 (m, 2H,ArH).

<Example 171>N-(1-Amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-2-naphthamide

Iron powder (35 mg, 0.60 mmoles), and 3 drops of conc. HCl were added toa solution ofN-(4b-hydroxy-7-isopropyl-4-nitro-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-2-naphthamide(0.10 g, 0.20 mmoles) in ethanol:water (10:1, 10 mL) and heated for 3hrs under reflux. After completion of the reaction, the reaction mixturewas washed with ethylacetate, filtered to remove iron powder, andextracted with ethylacetate and water. The organic layer was washed withbrine, dried, and concentrated, followed by separation and purificationby column chromatography (30% ethylacetate mixed with 40% hexane) toafford the title compound. 85 mg (90%).

¹H-NMR (300 MHz, CD₃OD) δ 1.20 (d, J=6.9 Hz, 6H, CH₃) 2.86 (sept, J=6.9Hz, 1H, CH) 6.68-6.72 (m, 2H, ArH) 6.90 (d, J=7.5 Hz, 1H, ArH) 7.03 (d,J=7.5 Hz, 1H, ArH) 7.44-7.59 (m, 4H, ArH) 7.89-7.97 (m, 4H, ArH) 8.45(s, 1H, ArH).

<Example 172>N-(1-Amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl-[1,1′-biphenyl]-4-carboxamide

Iron powder (33 mg, 0.58 mmoles), and 3 drops of conc. HCl were added toa solution ofN-(4b-hydroxy-7-isopropyl-4-nitro-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl-[,1′-biphenyl]-4-carboxamide (0.10 g, 0.19 mmoles) in ethanol:water (10:1,10 mL), and heated for 3 hrs under reflux. After completion of thereaction, the reaction mixture was washed with ethylacetate, filtered toremove iron powder, and extracted with ethylacetate and water. Theorganic layer was washed with brine, dried, and concentrated, followedby separation and purification by column chromatography (30%ethylacetate mixed with 30% hexane) to afford the title compound. 85 mg(90%).

¹H-NMR (300 MHz, CD₃OD) δ 1.19 (d, J=6.9 Hz, 6H, CH₃) 2.85 (sept, J=6.9Hz, 1H, CH) 6.68-6.76 (m, 2H, ArH) 6.89 (d, J=8.1 Hz, 1H, ArH) 7.02 (d,J=7.2 Hz, 1H, ArH) 7.34=7.45 (m, 5H, ArH) 7.53-7.59 (m, 4H, ArH)7.92-7.94 (m, 2H, ArH).

<Example 173>1-(1-Amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl-3-ethylurea

Fe (61 mg, 1.09 mmol and 2 drops of con. HCl were added to a solution of1-(1-nitro-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)-3-ethylurea(150 mg, 0.36 mmol) in a mixture of ethanol:water (10 ml:1 ml, andheated for 3 hrs under reflux. After concentration in a vacuum,purification by column chromatography (ethylacetate:n-hexane=1:1)afforded the title compound as a white solid (50 mg, 36%).

¹H-NMR (300 MHz, CD₃OD) δ 1.08 (t, J=7.1 Hz, 3H, CH₃), 1.19 (d, J=6.9Hz, 6H, CH₃), 2.80 (sep, J=6.9 Hz, 1H, CH), 3.32˜3.43 (m, 2H, CH₂), 6.60(d, J=1.3 Hz, 1H, ArH), 6.70 (d, J=8.2 Hz, 1H, ArH), 6.79 (dd, J=8.0 Hz,1.3 Hz, 1H, ArH), 6.91 (d, J=7.3 Hz, 1H, ArH), 7.36˜7.44 (m, 2H, ArH).

<Example 174>N-(1-Amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)tetrahydrofurane-2-carboxamide

Fe (38 mg, 0.68 mmol) and 2 drops of conc. HCl were added to a solutionof2N-(4b-hydroxy-7-isopropyl-1-nitro-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)tetrahydrofurane-2-carboxamide(100 mg, 0.23 mmol) in a mixture of ethanol:water (10 ml:1 ml), andheated for 3 hrs under reflux. After concentration in a vacuum,purification by column chromatography (ethylacetate:n-hexane=1:1)afforded the title compound as a white solid (70 mg, 75%).

¹H-NMR (300 MHz, CD₃OD) δ 1.14 (d, J=6.9 Hz, 6H, CH₃), 1.78˜2.08 (m, 3H,CH₂), 2.11˜2.23 (m, 1H, CH₂), 2.80 (sep, J=6.9 Hz, 1H, CH), 3.75˜3.87(m, 1H, OCH₂), 3.91˜4.04 (m, 1H, OCH₂), 4.30˜4.34 (m, 1H, OCH),6.63˜6.67 (m, 2H, ArH), 6.83 (d, J=7.9 Hz, 1H, ArH), 6.98 (d, J=7.3 Hz,1H, ArH), 7.32˜7.43 (m, 2H, ArH).

<Example 175>N-(1-Amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-2,2,2-trifluoroacetamide

Iron powder (0.10 g, 1.8 mmol), conc. HCl (0.03 ml), and water (0.8 ml)were added in that order to a solution of2,2,2-trifluoro-N-(4b-hydroxy-7-isopropyl-1-nitro-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)acetamide(0.11 g, 0.25 mmol) in absolute ethanol (8 ml), and heated for 3 hrsunder reflux. The reaction mixture was washed with ethylacetate, andfiltered to remove iron powder. The filtrate was concentrated in avacuum, and subjected for 30 min to column chromatography(ethylacetate:hexane=1:4) packed with Et₃N-treated silica gel to affordthe title compound. 90 mg (90%).

¹H-NMR (300 MHz, CD₃OD) δ 1.17 (d, J=6.9 Hz, 6H, CH₃) 2.80-2.85 (m, 1H,CH) 6.66-6.72 (m, 2H, ArH) 6.86 (d, J=7.8 Hz, 1H, ArH) 6.98 (d, J=7.2Hz, 1H, ArH) 7.33-7.36 (m, 1H, ArH) 7.45 (t, J=7.8 Hz, 1H, ArH).

<Example 176>N-(1-Amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)-1,1,1-trifluoromethanesulfonamide

Fe (60 mg, 1.08 mmol) and 2 drops of conc. HCl were added to a solutionof1,1,1-trifluoro-N-(4b-hydroxy-7-isopropyl-1-nitro-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)methanesulfonamide(170 mg, 0.36 mmol) in ethanol:water (10 ml:1 ml), and heated for 3 hrsunder reflux. After concentration in a vacuum, purification by columnchromatography (ethylacetate:n-hexane=1:1) afforded the title compoundas a white solid (140 mg, 88%).

¹H-NMR (300 MHz, CD₃OD) δ 1.16 (dd, J=6.9 Hz, 1.6 Hz, 6H, CH₃), 2.82(sep, J=6.9 Hz, 1H, CH), 6.64 (s, 1H, ArH), 6.67 (d, J=8.2 Hz, 1H, ArH),6.85 (d, J=7.7 Hz, 1H, ArH), 7.00 (d, J=7.4 Hz, 1H, ArH), 7.35 (d, J=8.0Hz, 1H, ArH), 7.45 (t, J=7.8 Hz, 1H, ArH).

<Example 177>N-(4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)formamide

A mixture of formic acid (2.5 mL) and acetic anhydride (5.0 mL) wasstirred at 80° C. for 30 min, and then cooled to room temperature beforea solution of9b-amino-4b-hydroxy-7-isopropyl-4bH-benzo[d]indeno[1,2-b]furan-10(9bH)-one(400 mg, 1.35 mmol) in DCM was added thereto. The resulting reactionmixture was stirred at room temperature for 1 hr, concentrated,extracted with ethylacetate and water, and concentrated again in avacuum. The concentrate was purified by silica gel column chromatography(30% ethylacetate mixed with 30% hexane) to afford the title compound.140 mg (32%).

¹H-NMR (300 MHz, CDCl₃) δ 1.16 (dd, J=6.9 Hz, J=2.4, 6H, CH₃) 2.82(hept, J=6.9 Hz, 1H, CH) 6.65 (s, 1H, ArH/NH/OH) 6.87 (d, J=7.8 1H, ArH)7.35 (d, J=7.8, 1H, ArH.) 7.65-7.80 (m, 2H, ArH) 7.81-7.9 (m, 2H, ArH)8.10 (s, 1H, NH/CHO).

<Example 178>1,1,1-Trifluoro-N-(4b-hydroxy-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)methanesulfonamide

Methanesulfonic anhydride (229 mg, 0.81 mmol) and triethylamine (123 mg,1.22 mmol) were added to a solution of4b-amino-9b-hydroxy-7-isopropyl-4b,9b-dihydro-5-oxa-indeno[2,1-a]-inden-10-one(200 mg, 0.68 mmol) in methylene chloride (10 ml), and stirred at roomtemperature for 4 hrs. After vacuum concentration, purification bycolumn chromatography (ethylacetate:hexane=1:2) afforded the titlecompound as a red solid (220 mg, 32%).

¹H-NMR (300 MHz, CDCl₃) δ 1.16 (d, J=6.9 Hz, 6H, CH₃), 2.81 (sep, J=6.9Hz, 1H, CH), 6.68 (s, 1H, ArH)), 6.81 (d, J=7.6 Hz, 1H, ArH), 7.54 (d,J=7.9 Hz, 1H, ArH), 7.51 (t, J=7.5 Hz, 1H, ArH), 7.75˜7.82 (m, 2H, ArH),8.01 (d, J=7.8 Hz, 1H, ArH).

<Example 179>N-(1-Amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-2-phenylacetamide

Iron powder (61 mg, 1.09 mmoles), and 3 drops of conc. HCl were added toa solution ofN-(4b-hydroxy-7-isopropyl-1-nitro-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl-2-phenylacetamide(0.10 g, 0.22 mmoles) in ethanol:water (10:1, 10 mL) and heated for 12hrs under reflux. The reaction mixture was filtered to remove ironpowder, and extracted with ethylacetate and water. The organic layer waswashed with brine, concentrated in a vacuum, and purified by silica gelcolumn chromatography (50% ethylacetate in hexane) to afford the titlecompound. 75 mg (81%).

¹H-NMR (300 MHz, CD₃OD) δ 1.17 (d, J=6.9 Hz, 6H, CH₃) 2.82 (sept, J=6.9Hz, 1H, CH) 3.59 (s, 2H, CH₂) 6.64 (br, 2H, ArH) 6.83 (br, 1H, ArH)6.96-6.98 (br, 1H, ArH) 7.19-7.41 (m, 6H, ArH).

<Example 180>(E)-N-(1-Amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-3-(3,4-dichlorophenylacrylamide

Iron powder (42 mg, 0.74 mmoles), and 3 drops of conc. HCl were added toa solution of(E)-3-(3,4-dichlorophenyl)-N-(4b-hydroxy-7-isopropyl-1-nitro-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)acrylamide(0.08 g, 0.15 mmoles) in ethanol:water (10:1, 10 mL) and heated for 12hrs under reflux. The reaction mixture was filtered to remove ironpowder, and extracted with ethylacetate and water. The organic layer waswashed with brine and concentrated in a vacuum. A small amount ofmethanol was added to the concentrate to form a precipitate which wasthen filtered to afford the title compound. 30 mg (80%).

¹H-NMR (300 MHz, CD₃OD) δ 1.18 (d, J=6.9 Hz, 6H, CH₃) 2.84 (sept, J=6.9Hz, 1H, CH) 6.66-6.79 (m, 3H, ArH) 6.86-6.88 (m, 1H, ArH) 6.99-7.01 (m,1H, ArH) 7.34-7.54 (m, 5H, ArH) 7.74 (s, 1H, ArH).

<Example 181>N-(1-Amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-4-(benzyloxy)benzamide

Iron powder (26 mg, 0.47 mmoles) and 2 drops of conc. HCl were added toa solution of4-benzyl-N-(4b-hydroxy-7-isopropyl-1-nitro-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)benzamide(0.05 g, 0.094 mmoles) in ethanol:water (10:1, 10 mL), and heated for 6hrs under reflux. After removal of the iron powder by filtration, thereaction mixture was extracted with ethylacetate and water. The organiclayer was washed with brine and concentrated in a vacuum. A small amountof methanol was added to the concentrate to form a precipitate which wasthen filtered to afford the title compound. 15 mg (32%).

¹H-NMR (300 MHz, CD₃OD) δ 1.18 (d, J=6.9 Hz, 6H, CH₃) 2.83 (sept, J=6.9Hz, 1H, CH) 5.12 (s, 2H, CH₂) 6.67 (s, 2H, ArH) 6.85 (s, 1H, ArH)7.00-7.03 (s, 3H, ArH) 7.18-7.43 (m, 7H, ArH) 7.80-7.83 (m, 2H, ArH).

<Example 182>2-([1,1′-Biphenyl]-4-yl)-N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)acetamide

Iron powder (31.3 mg, 0.56 mmoles), and 3 drops of conc. HCl were addedto a solution ofN-(4b-hydroxy-7-isopropyl-1-nitro-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)biphenyl-4-carboxamide(0.1 g, 0.18 mmoles) in ethanol:water (10:1, 10 mL), and heated for 4hrs under reflux. After removal of the iron powder by filtration, thereaction mixture was extracted with ethylacetate and water. The organiclayer was washed with brine and concentrated in a vacuum. A small amountof methanol was added to the concentrate to form a precipitate which wasthen filtered to afford the title compound. 50 mg (54%).

¹H-NMR (300 MHz, CD₃OD) δ 1.17 (d, J=6.9 Hz, 6H, CH₃) 2.83 (sept, J=6.9Hz, 1H, CH) 3.64 (s, 2H, CH₂) 6.65 (s, 2H, ArH) 6.83-6.86 (br, 1H, ArH)6.98 (br, 1H, ArH) 7.27-7.43 (m, 7H, ArH) 7.53-7.60 (m, 4H, ArH).

<Example 183>N-(1-Amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-2-methoxybenzamide

Iron powder (0.13 g, 2.46 mmol), conc. HCl (0.03 ml), and water (1 ml)was added in that order to a solution ofN-(4b-hydroxy-7-isopropyl-1-nitro-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-2-methoxybenzamide(0.16 g, 0.33 mmol) in absolute ethanol (10 ml), and heated for 2 hrsunder reflux. The reaction mixture was washed with ethylacetate, andfiltered to remove iron powder. The filtrate was purified for 30 bycolumn chromatography (ethylacetate:hexane=1:4) packed with Et₃N-treatedsilica gel to afford the title compound (80 mg, 54%).

¹H-NMR (300 MHz, CD₃OD) δ 1.22-1.23 (m, 6H, CH₃) 2.81-2.90 (sept, 1H,CH) 4.00 (s, 3H, OCH₃) 6.71 (s, 1H, ArH) 6.86 (s, 1H, ArH) 7.04-7.07 (m,2H, ArH) 7.12-7.15 (m, 2H, ArH) 7.50-7.55 (m, 3H, ArH) 7.94 (s, 1H,ArH).

<Example 184>tert-Butyl(2R)-1-(4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-ylamino)-1-oxopropan-2-ylcarbamate

EDCl (233 mg, 1.22 mmol) and HOBt (165 mg, 1.22 mmol) were added to asolution of Boc-L-alanine (231 mg, 1.22 mmol) in methylene chloride (20ml). 20 min later,4b-amino-9b-hydroxy-7-isopropyl-4b,9b-dihydro-5-oxa-indeno[2,1-a]-inden-10-one(300 mg, 1.02 mmol) was added to the solution, and stirred overnight atroom temperature. After completion of the reaction, the reaction mixturewas extracted with methylene chloride and water, and the organic layerwas dried over MgSO₄ and concentrated in a vacuum. Purification bycolumn chromatography (ethylacetate:n-hexane=1:2) afforded the titlecompound (368 mg, 77%).

¹H-NMR (300 MHz, CDCl₃) δ 1.16 (d, J=6.9 Hz, 6H, CH₃), 1.33˜1.47 (m, 9H,CH₃), 1.59 (s, 3H, CH₃), 2.81 (sep, J=6.9 Hz, 1H, CH), 4.19 (m, 1H),4.88 (m, 1H), 5.56 (s, 1H), 6.69 (s, 1H, ArH), 6.79˜6.83 (m, 1H, ArH),7.28 (m, 1H, ArH), 7.54 (t, J=7.4 Hz, 1H, ArH) 7.76˜7.81 (m, 2H, ArH),7.99 (d, J=7.6 Hz, 1H, ArH).

<Example 185>tert-Butyl(2R)-1-(4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-ylamino)-1-oxo-3-phenylpropan-2-ylcarbamate

EDCl (233 mg, 1.22 mmol) and HOBt (165 mg, 1.22 mmol) were added to asolution of Boc-L-phenylalanine (324 mg, 1.22 mmol) in methylenechloride (20 ml). 20 min later,4b-amino-9b-hydroxy-7-isopropyl-4b,9b-dihydro-5-oxa-indeno[2,1-a]-inden-10-one(300 mg, 1.02 mmol) was added to the solution, and stirred overnight atroom temperature. After completion of the reaction, the reaction mixturewas extracted with methylene chloride and water, and the organic layerwas dried over MgSO₄ and concentrated in a vacuum. Purification bycolumn chromatography (ethylacetate:n-hexane=1:2) afford the titlecompound (480 mg, 87%).

¹H-NMR (300 MHz, CDCl₃) δ 1.13 9 m, 6H, CH₃), 1.40 (m, 1H, CH),2.99′3.12 (m, 2H, CH₂), 4.29˜4.42 (m, 1H, CH), 4.90˜5.01 (m, 1H, CH),6.68 (s, 1H, ArH), 6.76˜6.84 (m, 1H, ArH), 7.10˜7.21 (m, 3H, ArH),7.27˜7.34 (m, 3H, ArH), 7.48˜7.55 (m, 1H, ArH), 7.75˜7.80 (m, 2H, ArH),7.96˜8.01 (m, 1H, ArH).

<Example 186>N-(1-Amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)-2-methylbenzamide

Fe (66 mg, 1.18 mmol) and 2 drops of conc. HCl were added to a solutionofN-(4b-hydroxy-7-isopropyl-1-nitro-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)-2-methylbenzamide(180 mg, 0.39 mmol) in ethanol:H₂O (20 ml:2 ml) and heated for 2.5 hrsunder reflux. After vacuum concentration, the reaction mixture waspurified by column chromatography (ethylacetate:n-hexane=1:3) to affordthe title compound as a yellow solid (134 mg, 80%).

¹H-NMR (500 MHz, CD₃OD) δ 1.16 (d, J=6.8 Hz, 6H, CH₃), 2.45 (s, 3H,ArH), 2.82 (sep, J=6.8 Hz, 1H, CH), 6.64 (s, 1H, ArH), 6.68 (d, J=8.3Hz, 1H, ArH), 6.85 (d, J=7.3 Hz, 1H, ArH), 7.03 (d, J=7.3 Hz, 1H, ArH),7.18˜7.22 (m, 2H, ArH), 7.30 (t, J=7.4 Hz, 1H, ArH), 7.41˜7.46 (m, 2H,ArH), 7.51 (d, J=7.3 Hz, 1H, ArH).

<Example 187>N-(1-Amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)-3-methylbenzamide

Fe (66 mg, 1.18 mmol) and 2 drops of conc. HCl were added to a solutionofN-(4b-hydroxy-7-isopropyl-1-nitro-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)-3-methylbenzamide(1800 mg, 0.39 mmol) in ethanol:H₂O (10 ml:1 ml), and heated for 3 hrsunder reflux. After vacuum concentration, the reaction mixture waspurified by column chromatography (ethylacetate:n-hexane=1:3) to affordthe title compound as a yellow solid (88 mg, 52%).

¹H-NMR (500 MHz, CD₃OD) δ 1.18 (dd, J=6.9 Hz, 1.4 Hz, 6H, CH₃), 2.36 (s,3H, ArH), 2.84 (sep, J=6.8 Hz, 1H, CH), 6.67˜6.70 (m, 2H, ArH),6.87˜6.88 (m, 1H, ArH), 7.02˜7.03 (m, 1H, ArH), 7.28˜7.35 (m, 2H, ArH),7.45 (m, 1H, ArH), 7.63 (d, J=7.6 Hz, 1H, ArH), 7.67 (s, 1H, ArH).

<Example 188>N-(1-Amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)-4-methylbenzamide

Fe (59 mg, 1.05 mmol) and 2 drops of conc. HCl were added to a solutionofN-(4b-hydroxy-7-isopropyl-1-nitro-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)-4-methylbenzamide(160 mg, 0.35 mmol in ethanol:H₂O (20 ml:2 ml) and heated for 4 hrsunder reflux. After vacuum concentration, the reaction mixture waspurified by column chromatography (ethylacetate:n-hexane=1:3) to affordthe title compound as a yellow solid (106 mg, 71%).

¹H-NMR (500 MHz, CD₃OD) δ 1.16 (d, J=6.8 Hz, 6H, CH₃), 2.35 (s, 3H,ArH), 2.81 (sep, J=6.8 Hz, 1H, CH), 6.65˜6.69 (m, 2H, ArH), 6.86 (d,J=7.4 Hz, 1H, ArH), 7.00 (d, J=7.4 Hz, 1H, ArH), 7.22 (d, J=7.5 Hz, 1H,ArH), 7.41˜7.46 (m, 2H, ArH), 7.74 (d, J=7.5 Hz, 1H, ArH).

<Example 189>Methyl-4-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-ylcarbamoyl)benzoate

Fe (93 mg, 1.67 mmol) and 2 drops of conc. HCl were added to a solutionof methyl4-(4b-hydroxy-7-isopropyl-1-nitro-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-ylcarbamoyl)benzoate(280 mg, 0.56 mmol) in ethanol:H₂O (20 ml:2 ml) and heated for 3 hrsunder reflux. After vacuum concentration, the reaction mixture waspurified by column chromatography (ethylacetate:n-hexane=1:3) to affordthe title compound as a yellow solid (186 mg, 71%).

¹H-NMR (500 MHz, CD₃OD) δ 1.16 (d, J=6.5 Hz, 6H, CH₃), 2.81 (sep, J=6.5Hz, 1H, CH), 3.89 (s, 3H, OCH₃), 6.65˜6.68 (m, 2H, ArH), 6.86 (d, J=7.4Hz, 1H, ArH), 7.02 (d, J=6.9 Hz, 1H, ArH), 7.41˜7.46 (m, 2H, ArH), 7.93(d, J=8.1 Hz, 2H, ArH), 8.04 (d, J=8.0 Hz, 2H, ArH).

<Example 190>N-(1-Amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-3-chlorobenzamide

Iron powder (0.17 g, 3.04 mmol), conc. HCl (0.03 ml), and water (1 ml)were added in that order to a solution of3-chloro-N-(4b-hydroxy-7-isopropyl-1-nitro-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)benzamide(0.20 g, 0.41 mmol) in absolute ethanol (10 ml), and heated for 2 hrsunder reflux. The reaction mixture was washed with ethylacetate andfiltered to remove the iron powder. The filtrate was alkalified withNaHCO₃, and washed many times with water, and the organic layer wasdried, filtered, and subjected for 30 min to column chromatography(ethylacetate:hexane=1:4) packed with Et₃N-treated silica gel to affordthe title compound. 90 mg (93%).

¹H-NMR (300 MHz, CD₃OD) δ 1.19 (dd, J=6.9, 2.1 Hz, 6H, CH₃) 2.85-2.87(sept, 1H, CH) 6.68-6.78 (m, 2H, ArH) 6.82-6.86 (m, 1H, ArH) 6.95-7.03(m, 1H, ArH) 7.38-7.60 (m, 4H, ArH) 7.77-7.79 (m, 1H, ArH) 7.87-7.90 (m,1H, ArH).

<Example 191>N-(1-Amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-3,5-dimethylbenzamide

Iron powder (0.04 g, 0.77 mmol), conc. HCl (0.01 ml), and water (0.5 ml)were added in that order to a solution ofN-(4b-hydroxy-7-isopropyl-1-nitro-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-3,5-dimethylbenzamide(50 mg, 0.10 mmol) in absolute ethanol (5 ml), and heated for 2 hrsunder reflux. The reaction mixture was washed with ethylacetate andfiltered to remove the iron powder. The filtrate was alkalified withNaHCO₃, and washed many times with water, and the organic layer wasdried, filtered, and subjected for 30 min to column chromatography(ethylacetate:hexane=1:4) packed with Et₃N-treated silica gel to affordthe title compound. 30 mg (68%).

¹H-NMR (300 MHz, CD₃OD) δ 1.18-1.20 (m, 6H, CH₃) 2.33 (s, 6H, CH₃)2.81-2.87 (sept, 1H, CH) 6.67-6.70 (m, 2H, ArH) 6.84-6.86 (m, 1H, ArH)7.03-7.05 (m, 1H, ArH) 7.18 (s, 1H, ArH) 7.46 (s, 4H, ArH).

<Example 192>N-(1-Amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-2,4,6-trichlorobenzamide

Iron powder (37 mg, 0.66 mmoles) and 2 drops of conc. HCl were added toa solution of2,4,6-trichloro-N-(4b-hydroxy-7-isopropyl-4-nitro-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)benzamide(0.12 g, 0.22 mmoles) in ethanol:water (10:1, 10 mL), and heated for 3hrs under reflux. After completion of the reaction, the reaction mixturewas washed with ethylacetate, filtered to remove iron powder, andextracted with ethylacetate and water. The organic layer was washed withbrine, dried, concentrated, and purified by column chromatography (30%ethylacetate mixed with 20% hexane) to afford the title compound. 85 mg(75%).

¹H-NMR (300 MHz, CD₃OD) δ 1.17 (d, J=6.9 Hz, 6H, CH₃) 2.83 (sept, J=6.9Hz, 1H, CH) 6.62-6.75 (m, 2H, ArH) 6.83 (m, 1H, ArH) 7.05 (m, 1H, ArH)7.36-7.54 (m, 3H, ArH) 7.89 (s, 1H, ArH).

<Example 193>N-(1-Amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)-2-fluoroacetamide

Fe (63 mg, 1.12 mmol) and 3 drops of conc. HCl were added to a solutionof2-fluoro-N-(4b-hydroxy-7-isopropyl-1-nitro-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)acetamide(150 mg, 0.37 mmol) in ethanol:H₂O (20 ml:2 ml), and heated for 2.5 hrsunder reflux. After vacuum concentration, the reaction mixture waspurified by column chromatography (EtOAc:hexane=1:1) to afford the titlecompound as a yellow solid (63 mg, 46%).

¹H-NMR (300 MHz, CD₃OD) δ 1.15 (d, J=6.3 Hz, 6H, CH₃), 2.82 (sep, J=6.3Hz, 1H, CH), 4.84 (d, J=45 Hz, 2H, CH₂F), 6.65˜6.68 (m, 2H, ArH),6.84˜6.87 (m, 1H, ArH), 6.97˜6.99 (m, 1H, ArH), 7.35˜7.45 (m, 2H, ArH).

<Example 194>N-(1-Amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)-2-chloroacetamide

Fe (45 mg, 0.79 mmol) and 3 drops of conc. HCl were added to a solutionof2-chloro-N-(4b-hydroxy-7-isopropyl-1-nitro-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)acetamide(110 mg, 0.26 mmol) in ethanol:H₂O (10 ml:1 ml), and heated for 3 hrsunder reflux. After vacuum concentration, the reaction mixture waspurified by column chromatography (EtOAc:hexane=1:1) to afford the titlecompound as a yellow solid (98 mg, 97%).

¹H-NMR (300 MHz, CD₃OD) δ 1.15 (d, J=6.9 Hz, 6H, CH₃), 2.81 (sep, J=6.9Hz, 1H, CH), 4.10 (d, J=4.0 Hz, 2H, CH₂Cl), 6.64˜6.67 (m, 2H, ArH),6.83˜6.87 (m, 1H, ArH), 6.98 (d, J=7.3 Hz, 1H, ArH), 7.35˜7.42 (m, 2H,ArH).

<Example 195>N-(1-Amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)-2,2-dichloroacetamide

Fe (36 mg, 0.65 mmol) and 2 drops of conc. HCl were added to a solutionof2,2-dichloro-N-(4b-hydroxy-7-isopropyl-1-nitro-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)acetamide(90 mg, 0.22 mmol) in ethanol:H₂O (10 ml:1 ml), and heated for 3 hrsunder reflux. After vacuum concentration, the reaction mixture waspurified by column chromatography (EtOAc:hexane=1:2) to afford the titlecompound as a yellow solid (62 mg, 74%).

¹H-NMR (300 MHz, CD₃OD) δ 1.15 (d, J=6.6 Hz, 6H, CH₃), 2.81 (sep, J=6.6Hz, 1H, CH), 6.06 (t, J=5.4 Hz, 1H, CHF₂), 6.65˜6.68 (m, 2H, ArH),6.84˜6.87 (m, 1H, ArH), 6.97˜6.99 (m, 1H, ArH), 7.35˜7.45 (m, 2H, ArH).

<Example 196>1-amino-9b-(4-butyl-1H-1,2,3-triazol-1-yl)-4b-hydroxy-7-isopropyl-4bH-indeno[1,2-b]benzofuran-10(9bH)-one

A solution of9b-(4-butyl-1H-1,2,3-triazol-1-yl)-4b-hydroxy-7-isopropyl-1-nitro-4bH-benzo[d]indeno[1,2-b]furan-10(9bH)-one(0.080 g, 0.18 mmol) in ethanol:water (10:1, 10 mL) was heated for 23hrs in the present of iron powder (38 mg, 0.68 mmol) under reflux. Thereaction mixture was washed with ethylacetate and filtered to removeiron powder, followed by extraction with ethylacetate and water.Separation and purification by silica gel column chromatography (30%ethylacetate mixed with 50% hexane) afforded the title compound. 50 mg(67%).

¹H-NMR (300 MHz, CD₃OD): δ 0.93 (t, J=7.2 Hz, 3H, CH₃) 1.23 (d, J=6.9Hz, 6H, CH₃) 1.33-1.41 (m, 2H, CH₂) 1.58-1.68 (m, 2H, CH₂) 2.69 (t,J=7.2 Hz, 2H, CH₂) 2.90 (sept, J=6.9 Hz, 1H, CH) 6.79 (br, 2H, ArH)6.98-7.03 (m, 2H, ArH) 7.22-7.41 (m, 2H, ArH) 7.50-7.55 (m, 1H, ArH).

<Example 197>N-(1-Amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)picolinamide

Iron powder (0.18 g, 3.2 mmol), conc. HCl (0.03 ml), and water (0.8 ml)were added in that order to a solution ofN-(4b-hydroxy-7-isopropyl-1-nitro-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)picolinamide(0.20 g, 0.44 mmol) in absolute ethanol (8 ml), and heated for 4 hrsunder reflux. The reaction mixture was washed with ethylacetate, andfiltered to remove iron powder. The filtrate was concentrated in avacuum and purified for 30 min by column chromatography(ethylacetate:hexane=1:2 to methylene chloride:MeOH=20:1) packed withEt₃N-treated silica gel to afford the title compound. 80 mg (43%).

¹H-NMR (300 MHz, CD₃OD) δ 1.20 (d, J=6.9 Hz, 6H, CH₃) 2.83-2.87 (m, 1H,CH) 6.70 (s, 2H, ArH) 6.89 (d, J=7.2 Hz, 1H, ArH) 7.02 (d, J=7.2 Hz, 1H,ArH) 7.45-7.48 (m, 2H, ArH) 7.55 (t, J=6.0 Hz, 1H, ArH) 7.90-7.97 (m,2H, ArH) 8.62 (d, J=3.6 Hz, 1H, ArH).

<Example 198>N-(1-Amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)nicotinamide

Iron powder (0.18 g, 3.2 mmol), conc. HCl (0.03 ml), and water (1 ml)were added in that order to a solution ofN-(4b-hydroxy-7-isopropyl-1-nitro-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)nicotinamide(0.20 g, 0.44 mmol) in absolute ethanol (10 ml), and heated for 2 hrsunder reflux. The reaction mixture was washed with ethylacetate, andfiltered to remove iron powder. The filtrate was concentrated in avacuum and purified for 30 min by column chromatography(ethylacetate:hexane=1:2 to methylene chloride:MeOH=20:1) packed withEt₃N-treated silica gel to afford the title compound. 140 mg (75%).

¹H-NMR (300 MHz, CD₃OD) δ 1.18 (d, J=6.9 Hz, 6H, CH₃) 2.79-2.88 (m, 1H,CH) 6.67-6.70 (m, 2H, ArH) 6.88 (d, J=7.8 Hz, 1H, ArH) 7.01 (d, J=7.2Hz, 1H, ArH) 7.43-7.51 (m, 3H, ArH) 8.25 (d, J=8.1 Hz, 1H, ArH) 8.65 (d,J=3.9 Hz, 1H, ArH) 9.00 (s, 1H, ArH).

<Example 199>N-(1-Amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)isonicotinamide

Iron powder (0.09 g, 16.3 mmol), conc. HCl (0.03 ml), and water (1 ml)were added in that order to a solution ofN-(4b-hydroxy-7-isopropyl-1-nitro-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)isonicotinamide(0.10 g, 0.22 mmol) in absolute ethanol (10 ml), and heated for 2 hrsunder reflux. The reaction mixture was washed with ethylacetate, andfiltered to remove iron powder. The filtrate was concentrated in avacuum and purified for 30 min by column chromatography(ethylacetate:hexane=1:1) packed with Et₃N-treated silica gel to affordthe title compound. 62 mg (68%).

¹H-NMR (300 MHz, CD₃OD) δ 1.18 (d, J=6.6 Hz, 6H, CH₃) 2.82-2.86 (m, 1H,CH) 6.67-6.71 (s, 2H, ArH) 6.89 (d, J=7.5 Hz, 1H, ArH) 7.01 (d, J=7.2Hz, 1H, ArH) 7.43-7.48 (m, 2H, ArH) 7.79-7.80 (m, 2H, ArH) 8.64-8.66 (m,2H, ArH).

<Example 200>N-(1-Amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)pyrazine-2-carboxamide

Iron powder (0.09 g, 1.63 mmol), conc. HCl (0.03 ml), and water (0.8 ml)were added in that order to a solution ofN-(4b-hydroxy-7-isopropyl-1-nitro-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)pyrazine-2-carboxamide(0.10 g, 0.22 mmol) in absolute ethanol (8 ml), and heated for 3 hrsunder reflux.

The reaction mixture was washed with ethylacetate, and filtered toremove iron powder. The filtrate was concentrated in a vacuum andpurified for 30 min by column chromatography (ethylacetate:hexane=1:1)packed with Et₃N-treated silica gel to afford the title compound. 90 mg(98%).

¹H-NMR (300 MHz, CD₃OD) δ 1.19 (d, J=6.6 Hz, 6H, CH₃) 2.80-2.89 (m, 1H,CH) 6.69-6.72 (m, 2H, ArH) 6.89 (d, J=8.1 Hz, 1H, ArH) 7.02 (d, J=7.2Hz, 1H, ArH) 7.43-7.49 (m, 2H, ArH) 8.66 (s, 1H, ArH) 8.78 (s, 1H, ArH)9.14 (s, 1H, ArH).

<Example 201>N-(1-Amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)furane-2-carboxamide

Iron powder (0.09 g, 1.68 mmol), conc. HCl (0.03 ml), and water (0.8 ml)were added in that order to a solution ofN-(4b-hydroxy-7-isopropyl-1-nitro-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)furane-2-carboxamide(0.10 g, 0.23 mmol) in absolute ethanol (8 ml), and heated for 2 hrsunder reflux. The reaction mixture was washed with ethylacetate, andfiltered to remove iron powder. The filtrate was concentrated in avacuum and purified for 30 min by column chromatography(ethylacetate:hexane=1:2) packed with Et₃N-treated silica gel to affordthe title compound. 52 mg (56%).

¹H-NMR (300 MHz, CD₃OD) δ 1.18 (d, J=6.9 Hz, 6H, CH₃) 2.79-2.85 (m, 1H,CH) 6.56 (d, J=1.5 Hz, 1H, ArH) 6.67 (s, 2H, ArH) 6.87 (d, J=6.0 Hz, 1H,ArH) 7.00 (d, J=6.0 Hz, 1H, ArH) 7.12 (d, J=3.3 Hz, 1H, ArH) 7.43-7.51(m, 2H, ArH) 7.64 (s, 1H, ArH).

<Example 202>N-(1-Amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)quinoline-8-carboxamide

Fe powder (35 mg, 0.60 mmoles), and 3 drops of conc. HCl were added to asolution ofN-(4b-hydroxy-7-isopropyl-4-nitro-0-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-ylquinoline-8-carboxamide(0.10 g, 0.20 mmoles) in ethanol:water (10:1, 10 mL), and heated for 3hrs under reflux. The reaction mixture was washed with ethylacetate, andfiltered to remove iron powder. The filtrate was concentrated in avacuum and purified by column chromatography (30% ethylacetate mixedwith 40% hexane) to afford the title compound. 80 mg (85%).

¹H-NMR (300 MHz, CD₃OD): δ 1.23 (dd, J=1.5 Hz, J=6.9 Hz, 6H, CH3) 2.84(sept, J=6.9 Hz, 1H, CH) 6.69 (s, 2H, ArH) 6.89 (s, 1H, ArH) 7.01 (s,1H, ArH) 7.45-7.67 (m, 3H, ArH) 7.72 (s, 1H, ArH) 8.14-8.17 (m, 1H, ArH)8.46-8.58 (m, 2H, ArH) 8.86 (s, 1H, ArH).

<Example 203>N-(1-Amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-ylquinoline-6-carboxamide

Fe powder (68 mg, 1.21 mmoles), and 3 drops of conc. HCl were added to asolution ofN-(4b-hydroxy-7-isopropyl-4-nitro-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-ylquinoline-6-carboxamide(0.20 g, 0.40 mmoles) in ethanol:water (10:1, 20 mL) and heated for 3hrs under reflux. The reaction mixture was washed with ethylacetate, andfiltered to remove iron powder. The filtrate was concentrated in avacuum, and recrystallized in 30% ethylacetate mixed with 30% hexane toafford the title compound. 130 mg.

¹H-NMR (300 MHz, CD₃OD): δ 1.19 (d, J=6.9 Hz, 6H, CH₃) 2.85 (sept, J=6.9Hz, 1H, CH) 6.70 (br, 2H, ArH) 6.88-6.90 (m, 1H, ArH) 7.03-7.06 (m, 1H,ArH) 7.48 (br, 2H, ArH) 7.58-7.62 (m, 1H, ArH) 8.05-8.08 (m, 1H, ArH)8.10-8.19 (m, 1H, ArH) 8.43-8.51 (m, 2H, ArH) 8.91-8.93 (m, 1H, ArH).

<Example 204>N-(1-Amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)benzofurane-2-carboxamide

Fe (69 mg, 1.24 mmol and 2 drops of conc. HCl were added to a solutionofN-(4b-hydroxy-7-isopropyl-1-nitro-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)benzofurane-2-carboxamide(200 mg, 0.41 mmol in ethanol:water (10 ml:1 ml) and heated for 3 hrsunder reflux. After vacuum concentration, the reaction mixture waspurified by column chromatography (ethylacetate:n-hexane=1:1) to affordthe title compound as a white solid (118 mg, 63%).

¹H-NMR (300 MHz, CD₃OD) δ 1.12 (d, J=6.7 Hz, 6H, CH₃), 2.77 (sep, J=6.7Hz, 1H, CH), 6.65˜6.67 (m, 2H, ArH), 6.85 (d, J=7.8 Hz, 1H, ArH), 7.03(d, J=7.3 Hz, 1H, ArH), 7.24 (t, J=7.4 Hz, 1H, ArH), 7.35˜7.43 (m, 2H,ArH), 7.46˜7.53 (m, 3H, ArH), 7.63 (d, J=7.7 Hz, 1H, ArH).

<Example 205>N-(1-Amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl-3-methylbenzofurane-2-carboxamide

Fe (67 mg, 1.2 mmol, and 2 drops of conc. HCl were added to a solutionofN-(4b-hydroxy-7-isopropyl-1-nitro-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)-3-methylbenzofurane-2-carboxamide(200 mg, 0.40 mmol in an ethanol:water (10 ml:1 ml) solvent, and heatedfor 23 hrs under reflux. After vacuum concentration, the reactionmixture was purified by column chromatography(ethylacetate:n-hexane=1:1) to afford the title compound as a whitesolid (162 mg, 86%).

¹H-NMR (300 MHz, CDCl₃) δ 1.20 (d, J=6.9 Hz, 6H, CH₃), 2.49 (s, 3H,CH₃), 2.85 (sep, J=6.9 Hz, 1H, CH), 6.70 (m, 2H, ArH), 6.89 (m, 1H,ArH), 7.03 (m, 1H, ArH), 7.31 (t, J=7.1 Hz, 1H, ArH), 7.42˜7.55 (m, 4H,ArH), 7.66 (d, J=7.7 Hz, 1H, ArH).

<Example 206>N-(1-Amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-4-methylthiazole-5-carboxamide

N-(4b-hydroxy-7-isopropyl-1-nitro-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl-4-methylthiazole-5-carboxamide(81 mg, 0.17 mmol was added to 5 ml of EtOH:H₂O (10:1) to form a paleyellow turbid solution to which Fe powder (29 mg, 0.51 mmol and one dropof conc. HCl were then added at room temperature, followed by stirringfor 2 hrs under reflux. The reaction mixture was filtered, concentrated,and purified by silica gel prep-TLC using EtOAc/Hx (1/1) to afford thetitle compound as a yellow solid (54 mg, 0.12 mmol, 73%).

¹H-NMR (300 MHz, CDCl₃) appears to be a mixture of 2 isomers) δ1.17-1.21 (m, 6H), 2.71 (s, 1H), 2.77 (2H), 2.78-2.89 (m, 1H), 5.56 (s,br, 1H), 5.58 (s, 0.6H), 5.75 (s, br, 0.8H), 6.63 (dd, J=8.2, 0.5 Hz,0.6H), 6.71-6.85 (m, 2H), 6.91-6.96 (m, 2H), 7.19 (dd, J=7.4, 0.5 Hz,0.6H), 7.28-7.32 (m, 1H), 7.48-7.60 (m, 1H), 8.72 (s, 0.4H), 8.75 (d,J=3.9 Hz, 1H).

<Example 207>(4R)—N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-2-oxothiazolidine-4-carboxamide

(4R)—N-(4b-hydroxy-7-isopropyl-1-nitro-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)-2-oxothiazolidine-4-carboxamide(100 mg, 0.213 mmol) was added to 5 ml of EtOH:H₂O (10:1) to form a paleyellow turbid solution to which Fe powder (36 mg, 0.64 mmol and twodrops of conc. HCl were then added at room temperature, followed bystirring for 2 hrs under reflux. The reaction mixture was filtered,concentrated, and purified by silica gel prep-TLC using EtOAc/Hx (1/1)to afford the title compound as a yellow solid (47 mg, 0.11 mmol, 50%).

¹H-NMR (300 MHz, CD₃OD) δ 1.170 (d, J=6.9 Hz, 3H), 1.173 (d, J=6.9 Hz,3H), 2.83 (heptet, J=6.9 Hz, 1H), 3.49-3.78 (m, 2H), 4.46-4.53 (m, 1H),6.66 (s, 1H), 6.70 (s, br, 1H), 6.85 (d, br, J=7.3 Hz, 1H), 7.00 (d,J=7.1 Hz, 1H), 7.35 (s, br, 1H), 7.39-7.51 (m, 1H).

<Example 208>N-(4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-1H-indole-2-carboxamide

A solution of indole-2-carboxylic acid (130 mg, 0.806 mmol) in anhydrousDCM was stirred, together with oxalyl chloride (0.08 mL, 0.967 mmol) anda catalyst, at room temperature for 1 hr. The reaction mixture wasconcentrated to obtain indole-2-acyl chloride.9b-amino-4b-hydroxy-7-isopropyl-4bH-benzo[d]indeno[1,2-b]furan-10(9bH)-one(190 mg, 0.643 mmol), indole-2-acylchloride (130 mg, 0.707 mmol), andtriethylamine (0.13 mL, 0.964 mmol) were dissolved in anhydrous DCM (2ml), and stirred at room temperature for 2 hrs. After extraction withDCM and water, the organic layer was washed with brine, dried oversodium sulfate, and concentrate in a vacuum. Separation and purificationby silica gel column chromatography (30% ethylacetate mixed with 20%hexane) afforded the title compound. 50 mg (38%).

¹H-NMR (300 MHz, CDCl₃) δ 1.18 (dd, J=7.2 Hz, 2.4 Hz, 6H, CH₃) 2.85(hept, J=6.9 Hz, 1H, CH) 6.68 (s, 1H, ArH/NH/OH) 6.92 (d, J=8.1, 1H,ArH) 7.01-7.06 (m, 1H, ArH) 7.19 (d, J=7.8 Hz, 1H, ArH) 7.22 (s, 1H,ArH) 7.38 (d, J=8.1 Hz, 1H, ArH) 7.47 (d, J=8.1 Hz, 1H, ArH) 7.59 (d,J=7.8 Hz, 1H, ArH) 7.74-7.88 (m, 3H, ArH).

<Example 209>N-(4b-Hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-1H-indole-3-carboxamide

Triethylamine (0.35 mL, 2.53 mmol) and indole-3-acylchloride (330 mg,0.186 mmol) were added to a solution of9b-amino-4b-hydroxy-7-isopropyl-4bH-benzo[d]indeno[1,2-b]furan-10(9bH)-one(500 mg, 1.69 mmol) in anhydrous DCM (5 ml), followed by stirring atroom temperature for 3 hrs. The reaction mixture was extracted with DCMand water, and the organic layer was washed with brine, dried oversodium sulfate, and concentrated in a vacuum. Separation andpurification by silica gel column chromatography (30% ethylacetate mixedwith 30% hexane) afforded the title compound. 60 mg (9%).

¹H-NMR (300 MHz, CDCl₃) δ 1.15 (dd, J=6.8 Hz, J=2.4, Hz 6H, CH₃) 2.78(hept, J=6.8 Hz, 1H, CH) 6.80 (d, J=8.1 Hz, 1H, ArH) 7.21 (s, 1H, ArH)7.37-7.58 (m, 2H, ArH) 7.55-7.58 (m, 1H, ArH) 7.75 (d, J=2.7 Hz, 1H,ArH) 7.813-7.850 (m, 2H, ArH) 7.99-8.07 (m, 2H, ArH), 8.95 (s, 1H,NH/ArH).

<Example 210>N-(4b-Hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)formamide

9b-Amino-4b-hydroxy-7-isopropyl-4bH-benzo[d]indeno[1,2-b]furan-10(9bH)-one(300 mg, 1.01 mmol) and 5-nitro-3-pyrazolecarboxylic acid (175 mg, 1.11mmol) were together dissolved in anhydrous DCM (3 ml) to which EDCl.HCl(290 mg, 1.52 mmol and HOBt (205 mg, 1.52 mmol were then added, followedby stirring overnight at room temperature. After extraction with DCM andwater, the organic layer was washed with brine, dried over sodiumsulfate, and concentrated in a vacuum. Separation and purification bysilica gel column chromatography (30% ethylacetate mixed with 40%hexane) afforded the title compound. 150 mg (34%).

¹H-NMR (300 MHz, CDCl₃) δ 1.17 (dd, J=6.9 Hz, J=2.4 Hz, 6H, CH₃) 2.84(hept, J=6.9 Hz, 1H, CH) 6.91 (d, J=8.1 Hz, 1H, ArH) 6.68 (s, 1H,ArH/NH/OH) 7.42 (d, J=8.1 Hz, 1H, ArH.) 7.60 (s, 2H, ArH.) 7.71-7.9 (m,2H, ArH) 7.9-7.93 (m, H, ArH) 7.93 (s, Br, 1H, ArH).

<Example 211>N-(4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-1-phenyl-5-(trifluoromethyl-1H-pyrazole-4-carboxamide

9b-Amino-4b-hydroxy-7-isopropyl-4bH-benzo[d]indeno[1,2-b]furan-10(9bH)-one(200 mg, 0.677 mmol) and1-H-phenyl-5-(trifluoromethyl)-1-H-pyrazole-4-carboxylic acid (190 mg,0.744 mmol) were dissolved in anhydrous DCM (2 ml) to which EDCl.HCl(190 mg, 1.015 mmol and HOBt (137 mg, 1.015 mmol were then added,followed by stirring overnight at room temperature. After extractionwith DCM and water, the organic layer was washed with brine, dried oversodium sulfate, and concentrated in a vacuum. Separation andpurification of the dark brown mixture by silica gel columnchromatography (30% ethylacetate mixed with 40% hexane) afforded thetitle compound. 50 mg (14%).

¹H-NMR (300 MHz, CDCl₃) δ 1.17 (dd. J=6.9 Hz, J=2.4 Hz, 6H, CH₃) 2.84(hept, 1H, CH) 6.68 (s, 1H, ArH/NH/OH) 6.90 (d, J=8.1 Hz, 1H, ArH)7.42-7.46 (m, 3H, ArH) 7.54-7.62 (m, 4H, ArH) 7.75-7.90 (m, 2H, ArH)7.90-8.10 (m, 1H, ArH) 8.10 (s, 1H, ArH/NH).

<Example 212>N-(1-Amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)-1H-indazole-3-carboxamide

N-(4b-hydroxy-7-isopropyl-1-nitro-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)-1H-indazole-3-carboxamide(190 mg, 0.39 mmol) was dissolved in an ethanol:water (10 ml:1 ml)solvent, and added with Fe (66 mg, 1.17 mmol) and then two drops ofconc. HCl. The reaction mixture was heated for 3 hrs under reflux. Aftervacuum concentration, purification by column chromatography(ethylacetate:n-hexane=1:2) afforded the title compound as a yellowsolid (92 mg, 52%).

¹H-NMR (300 MHz, CD₃OD) δ 1.18 (d, J=6.9 Hz, 6H, CH₃), 2.83 (sep, J=6.9Hz, 1H, CH), 6.67-6.72 (m, 2H, ArH), 6.88 (dd, J=7.9 Hz, 1.0 Hz, 1H,ArH), 7.03 (d, J=7.3 Hz, 1H, ArH), 7.19 (t, J=7.6 Hz, 1H, ArH), 7.38 (t,J=7.5 Hz, 1H, ArH), 7.43-7.57 (m, 3H, ArH), 8.09 (d, J=8.2 Hz, 1H, ArH).

<Example 213>N-(1-Amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)-2-(1H-tetrazol-1-yl)acetamide

N-(4b-hydroxy-7-isopropyl-1-nitro-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)-2-(1H-tetrazol-1-yl)acetamide(200 mg, 0.44 mmol) was dissolved in an ethanol:water (10 ml:1 ml)solvent, and added with Fe (74 mg, 1.32 mmol) and then with two drops ofcon. HCl. The reaction mixture was heated for 3 hrs under reflux. Aftervacuum concentration, purification by column chromatography(ethylacetate:n-hexane=2:1) afforded the title compound as a yellowsolid (104 mg, 56%).

¹H-NMR (300 MHz, CD₃OD) δ 1.17 (dd, J=6.9 Hz, 1.2 Hz, 6H, CH₃), 2.83(sep, J=6.9 Hz, 1H, CH), 5.36 (m, 2H, CH₂), 6.62˜6.66 (m, 2H, ArH), 6.87(dd, J=7.9 Hz, 1.1 Hz, 1H, ArH), 6.96 (d, J=7.3 Hz, 1H, ArH), 7.38˜7.43(m, 2H, ArH), 9.11 (s, 1H, ArH).

<Example 214>N-(1-Amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)quinoline-3-carboxamide

Iron powder (0.11 g, 1.9 mmol), conc. HCl (0.03 ml), and water (0.8 ml)were added in that order to a solution ofN-(4b-hydroxy-7-isopropyl-1-nitro-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)quinoline-3-carboxamide(0.13 g, 0.27 mmol) in absolute ethanol (8 ml), and heated for 1 hrunder reflux. The reaction mixture was washed with ethylacetate, andfiltered to remove iron powder. The filtrate was concentrated in avacuum and purified for 30 min by column chromatography(ethylacetate:hexane=1:4) packed with Et₃N-treated silica gel to affordthe title compound. 82 mg (65%).

¹H-NMR (300 MHz, CD₃OD) δ 1.19 (d, J=6.9 Hz, 6H, CH₃) 2.80-2.90 (sept,1H, CH) 6.70-6.74 (m, 2H, ArH) 6.89 (d, J=7.8 Hz, 1H, ArH) 7.04 (d,J=7.2 Hz, 1H, ArH) 7.48 (t, J=7.2 Hz, 2H, ArH) 7.68 (t, J=7.2 Hz, 1H,ArH) 7.87 (t, J=7.8 Hz, 1H, ArH) 8.02-8.08 (m, 2H, ArH) 8.86 (s, 1H,ArH) 9.23 (s, 1H, ArH).

<Example 215>N-(1-Amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)quinoline-4-carboxamide

Iron powder (0.12 g, 2.20 mmol), conc. HCl (0.03 ml), and water (1 ml)were added in that order to a solution ofN-(4b-hydroxy-7-isopropyl-1-nitro-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)quinoline-4-carboxamide(0.15 g, 0.30 mmol) in absolute ethanol (10 ml) and heated for 1 hrunder reflux. The reaction mixture was washed with ethylacetate, andfiltered to remove iron powder. The filtrate was concentrated in avacuum and purified for 30 min by column chromatography(ethylacetate:hexane=1:2) packed with Et₃N-treated silica gel to affordthe title compound. 0.12 g (92%).

¹H-NMR (300 MHz, CD₃OD) δ 1.19 (d, J=6.9 Hz, 6H, CH₃) 2.77-2.86 (sept,1H, CH) 6.66 (s, 1H, NH) 6.74-6.87 (m, 2H, ArH) 7.08 (d, J=7.4 Hz, 1H,ArH) 7.40-7.54 (m, 2H, ArH) 7.65-7.72 (m, 2H, ArH) 7.81 (t, J=7.8 Hz,1H, ArH) 8.06 (d, J=8.7 Hz, 1H, ArH) 8.40 (d, J=8.4 Hz, 1H, ArH) 8.90(d, J=4.1 Hz, 1H, ArH).

<Example 216>N-(1-Amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-5-methylthiophene-2-carboxamide

Iron powder (0.06 g, 1.24 mmol), conc. HCl (0.03 ml), and water (1 ml)were added in that order to a solution ofN-(4b-hydroxy-7-isopropyl-1-nitro-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)-5-methylthiophene-2-carboxamide(0.08 g, 0.17 mmol) in absolute ethanol (10 ml), and heated for 1 hrunder reflux. The reaction mixture was washed with ethylacetate, andfiltered to remove iron powder. The filtrate was concentrated in avacuum and purified for 30 min by column chromatography(ethylacetate:hexane=1:4) packed with Et₃N-treated silica gel to affordthe title compound. 67 mg (90%).

¹H-NMR (500 MHz, CD₃OD) δ 1.18 (d, J=6.9 Hz, 6H, CH₃) 2.53 (s, 3H, Me)2.75-2.84 (sept, 1H, CH) 6.57 (d, J=8.1 Hz, 1H, ArH) 6.64-6.71 (m, 2H,ArH) 6.76 (s, 1H, ArH) 6.87 (d, J=3.0 Hz, 1H, ArH) 7.24 (d, J=8.1 Hz,1H, ArH) 7.32 (t, J=8.1 Hz, 1H, ArH) 7.68 (d, J=3.6 Hz, 1H, ArH).

<Example 217>N-(1-Amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-2-methoxythiophene-3-carboxamide

Fe powder (0.06 g, 1.24 mmol), conc. HCl (0.03 ml), and (1 ml) wereadded in that order to a solution ofN-(4b-hydroxy-7-isopropyl-1-nitro-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)-2-methoxythiophene-3-carboxamide(0.28 g, 0.58 mmol), and heated for 1 hrs under reflux. The reactionmixture was washed with ethylacetate, and filtered to remove Fe powder.The filtrate was concentrated in a vacuum and purified for 30 min bycolumn chromatography (ethylacetate:hexane=1:4) packed with Et₃N-treatedsilica gel, followed by recrystallization in methylene chloride toafford the title compound. 77 mg (29%).

¹H-NMR (500 MHz, CD₃OD) δ 1.18 (d, J=6.9 Hz, 6H, CH₃) 2.75-2.84 (sept,1H, CH) 3.89 (s, 3H, OMe) 6.62-6.69 (m, 3H, ArH) 6.82-6.90 (m, 1H, ArH)6.96-7.05 (m, 1H, ArH) 7.38-7.47 (m, 2H, ArH) 7.95 (s, 1H, ArH).

<Example 218>N-(4b-Hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)picolinamide

A solution of picolinic acid (0.26 g, 2.1 mmol) in anhydrous MeCN (30ml) was stirred together with EDCl (0.45 g, 2.3 mmol) and HOBt (0.25 g,1.8 mmol) at room temperature for 10 min, and then together with9b-amino-4b-hydroxy-7-isopropyl-1-nitro-4bH-benzo[d]indeno[1,2-b]furan-10(9bH)-one(0.52 g, 1.76 mmol) at room temperature for 3 hrs. The reaction mixturewas diluted in methylene chloride, and washed many times with water, andthe organic layer was dried and filtered. Purification by columnchromatography (ethylacetate:hexane=1:4) afforded the title compound.0.53 g (76%).

¹H-NMR (300 MHz, CDCl₃) δ 1.16 (d, J=6.9 Hz, 6H, CH₃) 2.83 (sept, J=6.9Hz, 1H, CH) 5.69 (s, 1H) 6.75 (s, 1H) 6.83 (d, J=7.8 Hz, 1H, ArH) 7.36(d, J=7.8 Hz, 1H, ArH) 7.44-7.48 (m, 1H, ArH) 7.55-7.60 (m, 1H, ArH)7.80-7.86 (m, 3H, ArH) 8.02-8.09 (m, 2H, ArH) 8.60-8.61 (m, 1H, ArH)9.17 (s, 1H).

<Example 219>N-(4b-Hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)pyrimidine-4-carboxamide

A solution isonicotinic acid (0.26 g, 2.1 mmol) in anhydrous methylenechloride (20 ml) and dimethylformamide (10 ml) was stirred together withEDCl (0.45 g, 2.3 mmol) and HOBt (0.25 g, 1.8 mmol) for 10 min at roomtemperature, and then together with9b-amino-4b-hydroxy-7-isopropyl-1-nitro-4bH-benzo[d]indeno[1,2-b]furan-10(9bH)-one(0.46 g, 1.56 mmol) for 24 hrs at room temperature. The reaction mixturewas diluted in methylene chloride, and washed many times with water, andthe organic layer was dried and filtered. Purification by columnchromatography (ethylacetate:hexane=1:4) afforded the title compound.0.20 g (32%).

¹H-NMR (300 MHz, CD₃OD) δ 1.20 (d, J=6.9 Hz, 6H, CH₃) 2.81-2.90 (m, 1H,CH) 6.70 (brs, 1H, ArH) 6.91-6.93 (m, 1H, ArH) 7.42-7.47 (m, 1H, ArH)7.72-7.82 (m, 6H) 8.66-8.68 (m, 2H, ArH).

<Example 220>N-(4b-Hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)-2-(1H-tetrazol-5-yl)acetamide

A solution of 1H-tetrazole-5-acetic acid (131 mg, 1.02 mmol) inmethylene chloride (20 ml) and DMF (5 ml) was stirred together with EDCl(196 mg, 1.02 mmol) and HOBt (138 mg, 1.02 mmol) for 20 min, and thentogether with4b-amino-9b-hydroxy-7-isopropyl-4b,9b-dihydro-5-oxa-indeno[2,1-a]-inden-10-one(300 mg, 1.02 mmol) overnight at room temperature. After extraction withmethylene chloride and water, the organic layer was dried over MgSO₄ andconcentrated in a vacuum. Purification by column chromatography (20%methanol in methylene chloride) afforded the title compound as a whitesolid (136 mg, 33%).

¹H-NMR (300 MHz, CD₃OD) δ 1.16 (d, J=6.9 Hz, 6H, CH₃), 2.83 (sep, J=6.9Hz, 1H, CH), 3.97 (s, 2H, ArH), 6.66 (s, 1H, ArH), 6.88 (dd, J=8.0 Hz,1.1 Hz, 1H, ArH), 7.36 (d, J=7.9 Hz, 1H, ArH), 7.68˜7.79 (m, 3H, ArH).

<Example 221>N-(4b-Hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)-1H-benzo[d][1,2,3]triazole-5-carboxamide

A solution of benzotriazole-5-carboxylic acid (166 mg, 1.02 mmol) inmethylene chloride (20 ml) and DMF (5 ml) was reacted with EDCl (196 mg,1.02 mmol) and HOBt (138 mg, 1.02 mmol) for 20 min, and then stirredtogether with4b-amino-9b-hydroxy-7-isopropyl-4b,9b-dihydro-5-oxa-indeno[2,1-a]-inden-10-one(300 mg, 1.02 mmol) overnight at room temperature. After extraction withmethylene chloride and water, the organic layer was dried over MgSO₄ andconcentrated in a vacuum. Purification by column chromatography(ethylacetate:n-hexane=2:1) affordedN-(4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)-1H-benzo[d][1,2,3]triazole-5-carboxamideas a white solid (210 mg, 47%).

¹H-NMR (300 MHz, CD₃OD) δ 1.18 (d, J=6.9 Hz, 6H, CH₃), 2.85 (sep, J=6.9Hz, 1H, CH), 6.69 (d, J=1.2 Hz, 1H, ArH), 6.91 (dd, J=7.9 Hz, 1.2 Hz,1H, ArH), 7.48 (d, J=7.9 Hz, 1H, ArH), 7.62 (m, 1H, ArH), 7.79˜7.97 (m,5H, ArH), 8.49 (s, 1H, ArH).

<Example 222>N-(4b-Hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)-1H-1,2,4-triazole-3-carboxamide

1,2,4-triazole-3-carboxylic acid (116 mg, 1.02 mmol) was dissolved inmethylene chloride (20 ml) and DMF (5 ml), reacted with EDCl (196 mg,1.02 mmol) and HOBt (138 mg, 1.02 mmol) for 20 min, and then stirredtogether with4b-amino-9b-hydroxy-7-isopropyl-4b,9b-dihydro-5-oxa-indeno[2,1-a]-inden-10-one(300 mg, 1.02 mmol) overnight at room temperature. After extraction withmethylene chloride and water, the organic layer was dried over MgSO₄ andconcentrated in a vacuum. Purification by column chromatography (10%methanol in methylene chloride) afforded the title compound as a whitesolid. (141 mg, 35%).

¹H-NMR (300 MHz, CD₃OD) δ 1.17 (d, J=6.9 Hz, 6H, CH₃), 2.85 (sep, J=6.9Hz, 1H, CH), 6.68 (s, 1H, ArH), 6.90 (d, J=8.0 Hz, 1H, ArH), 7.45 (d,J=7.9 Hz, 1H, ArH), 7.60˜7.97 (m, 4H, ArH), 8.40 (s, 1H, ArH).

<Example 223>N-(4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)-5-nitrothiophene-2-carboxamide

5-Nitrothiophene-2-carboxylic acid (212 mg, 1.22 mmol) was dissolved inmethylene chloride (20 ml) and DMF (5 ml), reacted with EDCl (234 mg,1.22 mmol) and HOBt (165 mg, 1.22 mmol) for 20 min, and then stirredtogether with4b-amino-9b-hydroxy-7-isopropyl-4b,9b-dihydro-5-oxa-indeno[2,1-a]-inden-10-one(300 mg, 1.22 mmol) overnight at room temperature. After extraction withmethylene chloride and water, the organic layer was dried over MgSO₄ andconcentrated in a vacuum. Purification by column chromatography(ethylacetate:n-hexane=1:1) affordedN-(4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)-5-nitrothiophene-2-carboxamideas a yellow solid (80 mg, 17%).

¹H-NMR (300 MHz, CD₃OD) δ 1.17 (d, J=6.9 Hz, 6H, CH₃), 2.83 (sep, J=6.9Hz, 1H, CH), 6.67 (s, 1H, ArH), 6.90 (d, J=7.9 Hz, 1H, ArH), 7.43 (d,J=7.9 Hz, 1H, ArH), 7.71˜7.73 (m, 2H, ArH), 7.73˜7.93 (m, 4H, ArH).

<Example 224>N-(4b-Hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)-2,6-dioxo-1,2,3,6-tetrahydropyrimidine-4-carboxamide

Orotic acid (190 mg, 1.22 mmol) was dissolved in methylene chloride (20ml) and DMF (5 ml), reacted with EDCl (233 mg, 1.22 mmol) and HOBt (165mg, 1.22 mmol) for 20 min, and then stirred together with4b-amino-9b-hydroxy-7-isopropyl-4b,9b-dihydro-5-oxa-indeno[2,1-a]-inden-10-one(300 mg, 1.02 mmol) overnight at room temperature. After extraction withmethylene chloride and water, the organic layer was dried over MgSO₄ andconcentrated in a vacuum. Purification by column chromatography (10%methanol in methylene chloride) affordedN-(4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)-2,6-dioxo-1,2,3,6-tetrahydropyrimidine-4-carboxamideas a white solid (91 mg, 21%).

¹H-NMR (300 MHz, CD₃OD) δ 1.16 (d, J=6.9 Hz, 6H, CH₃), 2.83 (sep, J=6.9Hz, 1H, CH), 6.30 (s, 1H, ArH), 6.67 (s, 1H, ArH), 6.90 (d, J=8.0 Hz,1H, ArH), 7.39 (d, J=7.8 Hz, 1H, ArH), 7.60˜7.93 (m, 4H, ArH).

<Example 225>N-(4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)-2-oxo-2H-chromene-3-carboxamide

Coumarin-3-carboxylic acid (232 mg, 1.22 mmol) was dissolved inmethylene chloride (20 ml) and DMF (5 ml), reacted with EDCl (234 mg,1.22 mmol) and HOBt (165 mg, 1.22 mmol) for 20 min, and then stirredtogether with4b-amino-9b-hydroxy-7-isopropyl-4b,9b-dihydro-5-oxa-indeno[2,1-a]-inden-10-one(300 mg, 1.02 mmol) overnight at room temperature. After extraction withmethylene chloride and water, the organic layer was dried over MgSO₄ andconcentrated in a vacuum. Purification by column chromatography(ethylacetate:n-hexane=1:2) afforded the title compound as a white solid(377 mg, 79%).

¹H-NMR (300 MHz, CD₃OD) δ 1.19 (d, J=6.9 Hz, 6H, CH₃), 2.86 (sep, J=6.9Hz, 1H, CH), 6.70 (s, 1H, ArH), 6.92 (d, J=7.9 Hz, 1H, ArH), 7.41˜7.45(m, 3H, ArH), 7.72˜7.81 (m, 4H, ArH), 7.88˜7.89 (m, 2H, ArH), 8.74 (s,1H, ArH).

<Example 226>N-(4b-Hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)-2-oxo-2H-pyrane-5-carboxamide

Coumaric acid (171 mg, 1.22 mmol) was dissolved in methylene chloride(20 ml) and DMF (5 ml), reacted with EDCl (234 mg, 1.22 mmol) and HOBt(165 mg, 1.22 mmol) for 20 min, and then stirred together with4b-amino-9b-hydroxy-7-isopropyl-4b,9b-dihydro-5-oxa-indeno[2,1-a]-inden-10-one(300 mg, 1.02 mmol) overnight at room temperature. After extraction withmethylene chloride and water, the organic layer was dried over MgSO₄ andconcentrated in a vacuum. Purification by column chromatography(ethylacetate:n-hexane=1:1) afforded the title compound as a yellowsolid (60 mg, 14%).

¹H-NMR (300 MHz, CD₃OD) δ 1.16 (dd, J=6.9 Hz, 2.8 Hz, 6H, CH₃), 2.84(sep, J=6.9 Hz, 1H, CH), 5.61 (d, J=9.3 Hz, 1H, ArH), 6.78 (s, 1H, ArH),6.93 (dd, J=7.9 Hz, 1.0 Hz, 1H, ArH), 7.44 (d, J=7.9 Hz, 1H, ArH), 7.49(d, J=9.3 Hz, 1H, ArH), 7.63 (t, J=7.4 Hz, 1H, ArH), 7.81 (d, J=7.7 Hz,1H, ArH), 7.87˜7.92 (m, 2H, ArH), 8.01 (d, J=7.8 Hz, 1H, ArH).

<Example 227>N-(4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)-1H-benzo[d]imidazole-2-carboxamide

1H-benzimidazole-2-carboxylic acid (183 mg, 1.02 mmol) was dissolved inmethylene chloride (20 ml) and DMF (5 ml), reacted with EDCl (195 mg,1.02 mmol) and HOBt (138 mg, 1.02 mmol) for 20 min, and stirred togetherwith4b-amino-9b-hydroxy-7-isopropyl-4b,9b-dihydro-5-oxa-indeno[2,1-a]-inden-10-one(250 mg, 0.85 mmol) overnight at room temperature. After extraction withmethylene chloride and water, the organic layer was dried over MgSO₄ andconcentrated in a vacuum. Purification by column chromatography(ethylacetate:n-hexane=1:1) affordedN-(4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)-1H-benzo[d]imidazole-2-carboxamideas a white solid (210 mg, 56%).

¹H-NMR (300 MHz, CD₃OD) δ 1.19 (d, J=6.9 Hz, 6H, CH3), 2.86 (sep, J=6.9Hz, 1H, CH), 6.69 (s, 1H, ArH), 6.93 (dd, J=7.9 Hz, 1.2 Hz, 1H, ArH),7.32˜7.35 (m, 2H, ArH), 7.49 (d, J=7.9 Hz, 1H, ArH), 7.63˜7.64 (m, 4H,ArH), 7.89˜7.91 (m, 2H, ArH).

<Example 228>N-(1-Amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-3-(2-chloro-6-fluorophenyl)-5-methylisooxazole-4-carboxamide

5-(2-chloro-6-fluorophenyl)-N-(4b-hydroxy-7-isopropyl-1-nitro-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)-2-methylcyclopenta-1,4-dienecarboxamide(100 mg, 0.173 mmol) was added to 5 ml of EtOH:H₂O (10:1) to form a paleyellow turbid solution to which Fe powder (41 mg, 0.73 mmol) and threedrops of conc. HCl were then added at room temperature, followed bystirring for 2 hrs under reflux. The reaction mixture was filtered,concentrated, and purified by silica gel prep-TLC using EtOAc/Hx (1/1)to afford the title compound as a yellow solid (26.7 mg, 0.487 mmol,28%).

¹H-NMR (300 MHz, CD₃OD) δ 1.16 (d, J=6.9 Hz, 3H), 1.17 (d, J=6.8 Hz,3H), 2.72 (s, 3H), 2.73-2.88 (m, 1H), 6.62 (s, 1H), 6.63-6.82 (m, 2H),6.93-7.17 (m, 2H), 7.19-7.25 (m, 1H), 7.39-7.52 (m, 3H).

<Example 229>N-(4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-3-phenyl-1H-pyrazole-5-carboxamide

3-Phenyl-1H-pyrazole-5-carboxylic acid (116 mg, 0.616 mmol), HOBt (316mg, 2.34 mmol), and EDCl.HCl (441 mg, 2.30 mmol) were dissolved togetherin CH₂Cl₂(10 mL) to which a dilution of9b-amino-4b-hydroxy-7-isopropyl-4bH-benzo[d]indeno[1,2-b]furan-10(9bH)-one(500 mg, 1.69 mmol) in CH₂Cl₂ (5 mL) was then added, followed bystirring at room temperature for 2 hrs. The resulting yellow reactionmixture was mixed with water, and them extracted twice with CH₂Cl₂. Theorganic layer was dehydrated over anhydrous magnesium sulfate andconcentrated. The concentrate was purified by silica gel columnchromatography using EtOAc/Hx (1/3-1/2) to afford the title compound asa white solid (144.7 mg, 0.311 mmol, 50%).

¹H-NMR (300 MHz, CD₃OD) δ 1.13-1.23 (m, 6H), 2.77-2.92 (m, 1H), 6.68 (s,1H), 6.90 (d, J=7.9 Hz, 1H), 6.93-7.09 (m, 2H), 7.31-7.52 (m, 4H),7.52-8.07 (m, 6H).

<Example 230>N-(4b-Hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)nicotinamide

At 0° C., EDCl (0.48 g, 2.53 mmol),9b-amino-4b-hydroxy-7-isopropyl-1-nitro-4bH-benzo[d]indeno[1,2-b]furan-10(9bH)-one(0.50 g, 1.46 mmol), and HOBt (0.34 g, 2.53 mmol) were added in thatorder to a solution of nicotinic acid (0.31 g, 2.53 mmol) in anhydrousTHF (10 ml) and DMF (3 ml), followed by stirring at room temperature for2 days. During the reaction, solid products were washed with THF andwater, filtered, and dried to obtain the title compound. 0.33 g (49%).

¹H-NMR (300 MHz, CDCl₃) & 1.14 (d, J=6.3 Hz, 6H, CH₃) 2.71-2.82 (sept,1H, CH) 6.67 (s, 1H, NH) 6.80 (d, J=7.5 Hz, 1H, ArH) 7.30 (t, J=6.0 Hz,1H, ArH) 7.38 (d, J=7.8 Hz, 1H, ArH) 7.53 (t, J=7.2 Hz, 1H, ArH) 7.63(s, 1H, ArH) 7.73-7.82 (m, 2H, ArH) 7.91 (s, 1H, OH) 7.97 (d, J=7.8 Hz,1H, ArH) 8.10 (d, J=7.2 Hz, 1H, ArH) 8.56 (d, J=3.9 Hz, 1H, ArH) 8.96(s, 1H, ArH).

<Example 231>N-(1-Amino4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-2-oxo-2-(thiophen-2-yl)acetamide

Fe powder (0.30 g, 5.47 mmol), conc. HCl (0.03 ml), and water (1 ml)were added in that order to a solution ofN-(4b-hydroxy-7-isopropyl-1-nitro-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)thiophene-2-carboxamide(0.36 g, 0.75 mmol) in absolute ethanol (10 ml), and heated for 2 hrsunder reflux. The reaction mixture was washed with ethylacetate, andfiltered to remove Fe powder. The filtrate was concentrated in a vacuumand purified for 30 min by column chromatography(ethylacetate:hexane=1:4) packed with Et₃N-treated silica gel to affordthe title compound. 0.28 g (83%).

¹H-NMR (500 MHz, CD₃OD) δ 1.18 (d, J=6.9 Hz, 6H, CH₃) 2.81-2.86 (sept,1H, CH) 6.61-6.72 (m, 2H, ArH) 6.88 (d, J=7.5 Hz, 1H, ArH) 7.01 (d,J=7.2 Hz, 1H, ArH) 7.20 (t, J=5.1 Hz, 1H, ArH) 7.40 (d, J=7.5 Hz, 1H,ArH) 7.46 (t, J=7.8 Hz, 1H, ArH) 7.96 (d, J=4.5 Hz, 1H, ArH) 8.25 (d,J=2.7 Hz, 1H, ArH).

<Example 232>5-amino-N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)furane-2-carboxamide

Fe powder (0.32 g, 5.78 mmol), conc. HCl (0.03 ml), and (1 ml) wereadded in that order to a solution of5-amino-N-(4b-hydroxy-7-isopropyl-1-nitro-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)furane-2-carboxamide(0.38 g, 0.79 mmol) in absolute ethanol (10 ml), and heated for 2 hrsunder reflux. The reaction mixture was washed with ethylacetate, andfiltered to remove Fe powder. The filtrate was concentrated in a vacuumand purified by column chromatography (ethylacetate:hexane=1:4) packedwith Et₃N-treated silica gel to afford the title compound. 61 mg (48%).

¹H-NMR (300 MHz, CD₃OD) δ 1.25 (d, J=6.6 Hz, 6H, CH₃) 2.84-2.86 (sept,1H, CH) 6.75 (s, 1H, ArH) 6.88-6.94 (m, 2H, ArH) 7.08-7.11 (m, 1H, ArH)7.25 (t, J=7.5 Hz, 1H, ArH) 7.34-7.38 (m, 1H, ArH) 7.38-7.50 (m, 2H,ArH).

<Example 233>N-(1-Amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-1H-pyrrole-2-carboxamide

Fe powder (0.09 g, 1.6 mmol), conc. HCl (0.03 ml), and water (0.8 ml)were added in that order to a solution ofN-(4b-hydroxy-7-isopropyl-1-nitro-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)-1H-pyrrole-2-carboxamide(0.10 g, 0.23 mmol) in ethanol (8 ml), and heated for 2 hrs underreflux. The reaction mixture was washed with ethylacetate, and filteredto remove Fe powder. The filtrate was concentrated in a vacuum andpurified for 30 min by column chromatography (ethylacetate:hexane=1:2)packed with Et₃N-treated silica gel to afford the title compound. 90 mg(96%).

¹H-NMR (300 MHz, CD₃OD) & 1.18 (d, J=6.6 Hz, 6H, CH₃) 2.82-2.86 (sept,1H, CH) 6.16 (d, J=2.7 Hz, 1H, ArH) 6.88 (s, 1H, ArH) 6.70-6.74 (m, 1H,ArH) 6.85-6.90 (m, 3H, ArH) 7.03 (d, J=5.1 Hz, 1H, ArH) 7.30-7.46 (m,2H, ArH).

<Example 234>N-(1-Amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-2-methoxyisonicotinamide

Fe powder (0.12 g, 2.30 mmol), conc. HCl (0.03 ml), and water (1 ml)were added in that order to a solution ofN-(4b-hydroxy-7-isopropyl-1-nitro-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)-2-methoxyisonicotinamide(0.15 g, 0.31 mmol) in absolute ethanol (10 ml), and heated for 2 hrsunder reflux. The reaction mixture was washed with ethylacetate, andfiltered to remove Fe powder. The filtrate was concentrated in a vacuumand purified for 30 min by column chromatography(ethylacetate:hexane=1:4) packed with Et₃N-treated silica gel to affordthe title compound. 0.10 g (71%).

¹H-NMR (300 MHz, CD₃OD) & 1.17 (d, J=6.9 Hz, 6H, CH₃) 2.78-2.87 (sept,1H, CH) 3.91 (s, 3H, OMe) 6.67 (s, 1H, ArH) 6.74 (m, 1H, ArH) 6.85 (d,J=8.1 Hz, 1H, ArH) 7.02 (d, J=7.2 Hz, 1H, ArH) 7.19 (s, 1H, ArH) 7.29(d, J=5.4 Hz, 1H, ArH) 7.39-7.48 (m, 2H, ArH) 8.20 (d, J=4.8 Hz, 1H,ArH).

<Example 235>N-(1-Amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)benzo[b]thiophene-2-carboxamide

Fe (50 mg, 0.90 mmol) and 2 drops of con. HCl were sequentially added toa solution ofN-(4b-hydroxy-7-isopropyl-1-nitro-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)benzo[b]thiophene-2-carboxamide(150 mg, 0.30 mmol) in an ethanol:H₂O (10 ml:1 ml) solvent, and heatedfor 3 hrs under reflux. After vacuum concentration, purification bycolumn chromatography (ethylacetate:n-hexane=1:3) afforded the titlecompound as a yellow solid (76 mg, 54%).

¹H-NMR (500 MHz, CD₃OD) δ 1.19 (dd, J=6.9 Hz 1.2 Hz, 6H, CH₃), 2.85(sep, J=6.9 Hz, 1H, CH), 6.67˜6.70 (m, 2H, ArH), 6.90 (d, J=7.8 Hz, 1H,ArH), 7.01 (d, J=7.3 Hz, 1H, ArH), 7.39˜7.48 (m, 4H, ArH), 7.87 (d,J=7.5 Hz, 1H, ArH), 8.10 (s, 1H, ArH).

<Example 236>3-(2,6-dichlorophenyl)-N-(4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)-5-methylisooxazole-4-carboxamide

A solution of4b-amino-9b-hydroxy-7-isopropyl-4b,9b-dihydro-5-oxa-indeno[2,1-a]-inden-10-one(300 mg, 1.02 mmol) in methylene chloride (20 ml) was stirred overnighttogether with 3-(2,6-dichlorophenyl)-5-methyl-4-isooxazolecarbonylchloride (355 mg, 1.22 mmol) and triethylamine (0.3 ml, 1.83 mmol) atroom temperature. After completion of the reaction, concentration in avacuum and purification by column chromatography(ethylacetate:n-hexane=1:3) afforded the title compound (109 mg, 19%).

¹H-NMR (300 MHz, CDCl₃) δ 1.14 (dd, J=6.8 Hz, 6H, CH₃), 2.75 (s, 3H,CH₃), 2.78 (sep, J=6.8 Hz, 1H, CH), 6.02 (s, 1H), 6.56 (s, 1H), 6680 (s,1H, ArH), 6.75 (d, J=7.8 Hz, 1H, ArH), 6.88 (d, J=7.8 Hz, 1H, ArH), 7.48(t, J=7.5 Hz, 1H, ArH), 7.51˜7.68 (m, 4H, ArH), 7.76 (t, J=7.5 Hz, 1H,ArH), 7.98 (d, J=7.8 Hz, 1H, ArH).

<Example 237>N-(1-Amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)-9H-xanthene-9-carboxamide

Fe (37 mg, 0.66 mmol) and 2 drops of conc. HCl were sequentially addedto a solution ofN-(4b-hydroxy-7-isopropyl-1-nitro-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)-9H-xanthene-9-carboxamide(120 mg, 0.22 mmol) in an ethanol:water (10 ml:1 ml) solvent, and heatedfor 1.5 hrs under reflux. After vacuum concentration, purification bycolumn chromatography (ethylacetate:n-hexane=1:2) afforded the titlecompound as a yellow solid (65 mg, 57%).

¹H-NMR (500 MHz, CD₃OD) δ 1.18 (dd, J=6.9 Hz, 2.3 Hz, 6H, CH₃), 2.84(sep, J=6.9 Hz, 1H, CH), 5.09 (s, 1H, CH), 6.59 (s, 1H, ArH), 6.66 (s,1H, ArH), 6.88˜6.94 (m, 2H, ArH), 7.01˜7.06 (m, 3H, ArH), 7.15 (m, 1H,ArH), 7.22 (m, 1H, ArH), 7.28 (t, J=7.3 Hz, 1H, ArH), 7.36 (m, 1H, ArH),7.42˜7.45 (m, 2H, ArH), 7.54 (m, 1H, ArH).

<Example 238>N-(1-Amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)cinnoline-4-carboxamide

Fe (85 mg, 1.51 mmol) and 2 drops of conc. HCl were sequentially addedto a solution ofN-(4b-hydroxy-7-isopropyl-1-nitro-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)cinnoline-4-carboxamide(250 mg, 0.50 mmol) in an ethanol:water (20 ml:2 ml) solvent, and heatedfor 2 hrs under reflux. After vacuum concentration, purification bycolumn chromatography (ethylacetate:n-hexane=1:1) afforded the titlecompound as a yellow solid (230 mg, 99%).

¹H-NMR (300 MHz, CD₃OD) δ 1.16 (d, J=6.9 Hz, 6H, CH₃), 2.82 (sep, J=6.9Hz, 1H, CH), 6.68 (s, 1H, ArH), 6.72 (d, J=8.1 Hz, 1H, ArH), 6.86 (d,J=8.1 Hz, 1H, ArH), 7.07 (d, J=7.1 Hz, 1H, ArH), 7.44˜7.51 (m, 2H, ArH),7.90˜8.01 (m, 2H, ArH), 8.44˜8.51 (m, 2H, ArH), 9.46 (s, 1H, ArH).

<Example 239>N-(4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)cinnoline-4-carboxamide

A solution of cinnoline-4-carboxylic acid (183 mg, 1.02 mmol) inmethylene chloride (20 ml) was reacted with EDCl (195 mg, 1.02 mmol) andHOBt (138 mg, 1.02 mmol) for 20 min and then stirred, together with4b-amino-9b-hydroxy-7-isopropyl-4b,9b-dihydro-5-oxa-indeno[2,1-a]-inden-10-one(250 mg, 0.85 mmol), overnight at room temperature. After extractionwith methylene chloride and water, the organic layer was dried overMgSO₄ and concentrated in a vacuum. Purification by columnchromatography (ethylacetate:n-hexane=1:1) afforded the title compoundas a white solid (290 mg, 63%).

¹H-NMR (300 MHz, CD₃OD) δ 1.15 (d, J=6.8 Hz, 6H, CH₃), 2.82 (sep, J=6.8Hz, 1H, CH), 6.69 (s, 1H, ArH), 6.89 (d, J=7.8 Hz, 1H, ArH), 7.45 (d,J=7.9 Hz, 1H, ArH), 7.65 (m, 1H, ArH), 7.85˜8.03 (m, 5H, ArH) 8.42 (d,J=8.0 Hz, 1H, ArH), 8.51 (d, J=8.4 Hz, 1H, ArH), 9.45 (s, 1H, ArH).

<Example 240>N-(4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)-1H-benzo[d]imidazole-5-carboxamide

5-benzimidazolecarboxylic acid (198 mg, 1.22 mmol) was dissolved inmethylene chloride (20 ml) and DMF (3 ml), reacted with, EDCl (233 mg,1.22 mmol) and HOBt (165 mg, 1.22 mmol) for 20 min, and then stirred,together with4b-amino-9b-hydroxy-7-isopropyl-4b,9b-dihydro-5-oxa-indeno[2,1-a]-inden-10-one(300 mg, 1.02 mmol), overnight at room temperature. After extractionwith methylene chloride and water, the organic layer was dried overMgSO₄ and concentrated in a vacuum. Purification by columnchromatography (MC in MeOH 10%) afforded the title compound as a whitesolid (207 mg, 46%).

¹H-NMR (300 MHz, CD₃OD) δ 1.18 (d, J=6.8 Hz, 6H, CH₃), 2.85 (sep, J=6.8Hz, 1H, CH), 6.68 (s, 1H, ArH), 6.92 (d, J=7.8 Hz, 1H, ArH), 7.49 (d,J=8.1 Hz, 1H, ArH), 7.61˜7.64 (m, 2H, ArH), 7.78˜7.83 (m, 3H, ArH), 7.96(d, J=7.5 Hz, 1H, ArH), 8.19 (s, 1H, ArH), 8.26 (s, 1H, ArH).

<Example 241>N-(1-Amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)acridine-9-carboxamide

Fe (46 mg, 0.82 mmol) and 2 drops of conc. HCl were sequentially addedto a solution ofN-(4b-hydroxy-7-isopropyl-1-nitro-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)acridine-9-carboxamide(150 mg, 0.27 mmol) in an ethanol:water (20 ml:2 ml) solvent and heatedfor 2 hrs under reflux. After vacuum concentration, purification bycolumn chromatography (ethylacetate:n-hexane=1:1) afforded the titlecompound as a yellow solid (90 mg, 65%).

¹H-NMR (500 MHz, CD₃OD) δ 1.14 (d, J=6.9 Hz, 6H, CH₃), 2.80 (sep, J=6.9Hz, 1H, CH), 6.67 (s, 1H, ArH), 6.74 (d, J=7.4 Hz, 1H, ArH), 6.81 (d,J=7.5 Hz, 1H, ArH), 7.13 (d, J=6.8 Hz, 1H, ArH), 7.42 (d, J=7.0 Hz, 1H,ArH), 7.51 (t, J=7.5 Hz, 1H, ArH), 7.62 (t, J=7.1 Hz, 1H, ArH), 7.80 (t,J=7.0 Hz, 1H, ArH), 7.84 (t, J=6.8 Hz, 1H, ArH), 8.13˜8.18 (m, 2H, ArH),8.56 (d, J=7.5 Hz, 1H, ArH), 8.72 (d, J=7.5 Hz, 1H, ArH).

<Example 242>N-(1-Amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)-4-nitro-1H-pyrazole-3-carboxamide

Fe (76 mg, 1.36 mmol) and 2 drops of conc. HCl were sequentially addedto a solution ofN-(4b-hydroxy-7-isopropyl-1-nitro-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)-4-nitro-1H-pyrazole-3-carboxamide(217 mg, 0.45 mmol) in an ethanol:H₂O (20 ml:2 ml) solvent and heatedfor 2 hrs under reflux. After vacuum concentration, purification bycolumn chromatography (methanol in methylene chloride 5%) afforded thetitle compound as a yellow solid (134 mg, 71%).

¹H-NMR (300 MHz, CD₃OD) δ 1.18 (d, J=6.8 Hz, 6H, CH₃), 2.84 (sep, J=6.8Hz, 1H, CH), 6.66˜6.68 (m, 2H, ArH), 6.87˜6.89 (m, 1H, ArH), 7.01˜7.03(m, 1H, ArH), 7.44˜7.48 (m, 2H, ArH), 8.48 (s, 1H, ArH).

<Example 243>N-(1-Amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)-4-methylpicolinamide

Fe (109 mg, 1.96 mmol) and 2 drops of conc. HCl were sequentially addedto a solution ofN-(4b-hydroxy-7-isopropyl-1-nitro-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)-4-methylpicolinamide(300 mg, 0.65 mmol) in an ethanol:H₂O (20 ml:2 ml) solvent and heatedfor 3 hrs under reflux. After vacuum concentration, purification bycolumn chromatography (ethylacetate:n-hexane=1:3) afforded the titlecompound as a yellow solid (113 mg, 40%).

¹H-NMR (300 MHz, CD₃OD) δ 1.14 (d, J=6.7 Hz, 6H, CH₃), 2.35 (s, 3H,CH₃), 2.79 (sep, J=6.7 Hz, 1H, CH), 6.65˜6.66 (m, 2H, ArH), 6.83 (d,J=5.9 Hz, 1H, ArH), 7.03 (d, J=6.2 Hz, 1H, ArH), 7.30 (d, J=4.1 Hz, 1H,ArH), 7.42˜7.45 (m, 2H, ArH), 7.78 (d, 1H, ArH), 8.40 (d, J=4.6 Hz, 1H,ArH).

<Example 244>N-(1-Amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)-4-(trifluoromethyl)picolinamide

Fe (104 mg, 1.87 mmol) and 2 drops of conc. HCl were sequentially addedto a solution ofN-(4b-hydroxy-7-isopropyl-1-nitro-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)-4-(trifluoromethyl)picolinamide(320 mg, 0.62 mmol) in an ethanol:H₂O (20 ml:2 ml) solvent and heatedfor 4 hrs under reflux. After vacuum concentration, purification bycolumn chromatography (ethylacetate:n-hexane=1:2) afforded the titlecompound as a yellow solid (127 mg, 42%).

¹H-NMR (300 MHz, CD₃OD) δ 1.15 (d, J=6.8 Hz, 6H, CH₃), 2.79 (sep, J=6.8Hz, 1H, CH), 6.65˜6.75 (m, 2H, ArH), 6.85 (d, J=6.7 Hz, 1H, ArH), 7.03(d, J=6.7 Hz, 1H, ArH), 7.43˜7.51 (m, 2H, ArH), 7.81 (d, J=4.6 Hz, 1H,ArH), 8.20 (s, 1H, ArH), 8.82 (d, J=4.6 Hz, 1H, ArH).

<Example 245>N-(1-Amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)-5-cyanopicolinamide

Fe (107 mg, 1.91 mmol) and 2 drops of conc. HCl were sequentially addedto a solution of5-cyano-N-(4b-hydroxy-7-isopropyl-1-nitro-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)picolinamide(300 mg, 0.64 mmol) in an ethanol:H₂O (20 ml:2 ml) solvent and heatedfor 4 hrs under reflux. After vacuum concentration, purification bycolumn chromatography (ethylacetate:n-hexane=1:2) afforded the titlecompound as a yellow solid (40 mg, 14%).

¹H-NMR (300 MHz, CD₃OD) δ 1.17 (d, J=6.8 Hz, 6H, CH₃), 2.83 (sep, J=6.8Hz, 1H, CH), 6.68˜6.73 (m, 2H, ArH), 6.86 (d, J=7.3 Hz, 1H, ArH), 7.02(d, J=6.8 Hz, 1H, ArH), 8.11 (d, J=8.1 Hz, 1H, ArH), 8.31 (d, J=8.1 Hz,1H, ArH), 8.92 (s, 1H, ArH).

<Example 246>N-(1-Amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)-3-chloropicolinamide

Fe (157 mg, 2.81 mmol) and 2 drops of conc. HCl were sequentially addedto a solution of3-chloro-N-(4b-hydroxy-7-isopropyl-1-nitro-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)picolinamide(450 mg, 0.94 mmol) in an ethanol:H₂O (20 ml:2 ml) solvent and heatedfor 2.5 hrs under reflux. After vacuum concentration, purification bycolumn chromatography (ethylacetate:n-hexane=1:2) afforded the titlecompound as a yellow solid (168 mg, 40%).

¹H-NMR (500 MHz, CD₃OD) δ 1.18 (dd, J=6.9 Hz, 2.2 Hz, 6H, CH₃), 2.83(sep, J=6.9 Hz, 1H, CH), 6.67 (m, 2H, ArH), 6.85˜6.86 (m, 1H, ArH),7.02˜7.03 (m, 1H, ArH), 7.44˜7.51 (m, 3H, ArH), 7.93 (dd, J=8.1 Hz, 1.1Hz, 1H, ArH), 8.51 (d, J=4.1 Hz, 1H, ArH).

<Example 247>N-(1-Amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)-4-methoxyquinoline-2-carboxamide

Fe (140 mg, 2.51 mmol) and 2 drops of conc. HCl were sequentially addedto a solution ofN-(4b-hydroxy-7-isopropyl-1-nitro-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)-4-methoxyquinoline-2-carboxamide(440 mg, 0.84 mmol) in an ethanol:H₂O (20 ml:2 ml) solvent and heatedfor 3 hrs under reflux. After vacuum concentration, purification bycolumn chromatography (ethylacetate:n-hexane=1:3) afforded the titlecompound as a yellow solid (52 mg, 12%).

¹H-NMR (300 MHz, CD₃OD) δ 1.22 (d, J=6.9 Hz, 6H, CH₃), 2.87 (sep, J=6.9Hz, 1H, CH), 4.11 (s, 3H, OCH₃), 6.72˜6.74 (m, 2H, ArH), 6.90˜6.93 (m,1H, ArH), 7.03˜7.06 (m, 1H, ArH), 7.45˜7.55 (m, 3H, ArH), 7.61 (t, J=7.8Hz, 1H, ArH), 7.77 (t, J=7.8 Hz, 1H, ArH), 8.05 (d, J=8.1 Hz, 1H, ArH),8.24 (d, J=7.8 Hz, 1H, ArH).

<Example 248>N-(1-Amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)isoquinoline-3-carboxamide

Fe powder (0.16 g, 2.92 mmol), conc. HCl (0.04 ml), and water (1 ml)were added in that order to a solution ofN-(4b-hydroxy-7-isopropyl-1-nitro-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)isoquinoline-3-carboxamide(0.20 g, 0.40 mmol) in absolute ethanol (10 ml), and heated for 2 hrsunder reflux. The reaction mixture was washed with ethylacetate, andfiltered to remove Fe powder. The filtrate was alkalified with NaHCO₃,and washed many times with water. The organic layer was dried andfiltered. This filtrate was purified for 30 min by column chromatography(ethylacetate:hexane=1:4) packed with Et₃N-treated silica gel to affordthe title compound. 90 mg (50%).

¹H-NMR (300 MHz, CD₃OD) b 1.20 (d, J=6.9 Hz, 6H, CH₃) 2.81-2.88 (sept,1H, CH) 6.70-6.80 (m, 2H, ArH) 6.85-6.90 (m, 1H, ArH) 7.07-7.10 (m, 1H,ArH) 7.45-7.52 (m, 2H, ArH) 7.77-7.87 (m, 2H, ArH) 8.05 (d, J=7.5 Hz,1H, ArH) 8.17 (d, J=8.1 Hz, 1H, ArH) 8.43 (s, 1H, ArH) 9.27 (s, 1H,ArH).

<Example 249>N-(1-Amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-2-methylisonicotinamide

Fe powder (0.17 g, 3.17 mmol), conc. HCl (0.04 ml) and water (1 ml) wereadded in that order to a solution ofN-(4b-hydroxy-7-isopropyl-1-nitro-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)-2-methylisonicotinamide(0.20 g, 0.43 mmol) in absolute ethanol (10 ml), and heated for 2 hrsunder reflux. The reaction mixture was washed with ethylacetate, andfiltered to remove Fe powder. The filtrate was alkalified with NaHCO₃,and washed many times with water. The organic layer was dried andfiltered. The filtrate was purified for 30 min by column chromatography(ethylacetate:hexane=1:2) packed with Et₃N-treated silica gel to affordthe title compound. 0.13 g (72%).

¹H-NMR (300 MHz, CD₃OD) b 1.17 (d, J=6.9 Hz, 6H, CH₃) 2.56 (s, 3H, CH₃)6.67-6.70 (m, 2H, ArH) 6.87 (d, J=6.9 Hz, 1H, ArH) 7.01 (d, J=6.3 Hz,1H, ArH) 7.42-7.44 (m, 2H, ArH) 7.58 (d, J=5.1 Hz, 1H, ArH) 7.67 (s, 1H,ArH) 8.49 (d, J=5.1 Hz, 1H, ArH).

<Example 250>N-(1-Amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-3-fluoroisonicotinamide

Fe powder (0.26 g, 4.72 mmol), conc. HCl (0.04 ml), and water (1 ml)were added in that order to a solution of3-fluoro-N-(4b-hydroxy-7-isopropyl-1-nitro-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)isonicotinamide(0.30 g, 0.64 mmol) in absolute ethanol (10 ml), and heated for 2 hrsunder reflux. The reaction mixture was washed with ethylacetate, andfiltered to remove Fe powder. The filtrate was alkalified with NaHCO₃,and washed many times with water. The organic layer was dried andfiltered, followed by purification for 30 min by column chromatography(ethylacetate:hexane=1:2) packed with Et₃N-treated silica gel to affordthe title compound. 0.16 g (84%).

¹H-NMR (300 MHz, CD₃OD) δ 1.16 (d, J=6.9 Hz, 6H, CH₃) 2.80-2.84 (m, 1H,CH) 6.67-6.72 (m, 2H, ArH) 6.86 (d, J=5.7 Hz, 1H, ArH) 7.02 (d, J=6.3Hz, 1H, ArH) 7.43-7.46 (m, 2H, ArH) 7.66 (t, J=5.1 Hz, 1H, ArH) 8.46 (d,J=4.5 Hz, 1H, ArH) 8.56 (s, 1H, ArH).

<Example 251>N-(1-Amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-3-chloroisonicotinamide

Fe powder (0.16 g, 3.04 mmol), conc. HCl (0.04 ml), and water (1 ml)were added in that order to a solution of3-chloro-N-(4b-hydroxy-7-isopropyl-1-nitro-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)isonicotinamide(0.20 g, 0.41 mmol) in absolute ethanol (10 ml), and heated for 2 hrsunder reflux. The reaction mixture was washed with ethylacetate, andfiltered to remove Fe powder. The filtrate was alkalified with NaHCO₃,and washed many times with water. The organic layer was dried andfiltered, followed by purification for 30 min by column chromatography(ethylacetate:hexane=1:2) packed with Et₃N-treated silica gel to affordthe title compound. 0.15 g (83%).

¹H-NMR (300 MHz, CD₃OD) δ 1.16 (d, J=6.6 Hz, 6H, CH₃) 2.77-2.86 (m, 1H,CH) 6.66-6.71 (m, 2H, NH, ArH) 6.84 (d, J=7.5 Hz, 1H, ArH) 7.03 (d,J=6.9 Hz, 1H, ArH) 7.41-7.49 (m, 2H, ArH) 7.57 (d, J=4.8 Hz, 1H, ArH)8.52 (d, J=4.8 Hz, 1H, ArH) 8.62 (s, 1H, ArH).

<Example 252>N-(1-Amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-1-methyl-1H-imidazole-2-carboxamide

Fe powder (0.10 g, 1.95 mmol), conc. HCl (0.04 ml), and water (1 ml)were added in that order to a solution ofN-(4b-hydroxy-7-isopropyl-1-nitro-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)-1-methyl-1H-imidazole-2-carboxamide(0.12 g, 0.26 mmol) in absolute ethanol (10 ml), and heated for 2 hrsunder reflux. The reaction mixture was washed with ethylacetate, andfiltered to remove Fe powder. The filtrate was alkalified with NaHCO₃,and washed many times with water. The organic layer was dried andfiltered, followed by purification for 30 min by column chromatography(ethylacetate:hexane=1:2) packed with Et₃N-treated silica gel to affordthe title compound. 20 mg (18%).

¹H-NMR (300 MHz, CD₃OD) δ 1.18 (d, J=6.9 Hz, 6H, CH₃) 2.79-2.87 (m, 1H,CH) 3.89 (m, 3H, CH₃) 6.67 (s, 1H, ArH) 6.73 (d, J=6.3 Hz, 1H, ArH) 6.86(d, J=7.1 Hz, 1H, ArH) 7.00-7.02 (m, 2H, ArH) 7.20 (s, 1H, ArH)7.39-7.48 (m, 2H, ArH).

<Example 253>2-((1-Amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)carbamoyl)pyridine1-oxide

Fe (109 mg, 1.95 mmol) and 2 drops of conc. HCl were sequentially addedto a solution of2-((4b-hydroxy-7-isopropyl-1-nitro-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)carbamoyl)pyridine1-oxide (300 mg, 0.65 mmol) in an ethanol:H₂O (20 ml:2 ml) solvent andheated for 2 hrs under reflux. After vacuum concentration, purificationby column chromatography (EtOAc:hexane=2:1) afforded the title compoundas a yellow solid (110 mg, 39%).

¹H-NMR (300 MHz, CD₃OD) δ 1.19 (d, J=6.9 Hz, 6H, CH₃), 2.84 (sep, J=6.9Hz, 1H, CH), 6.68˜6.76 (m, 2H, ArH), 6.87 (d, J=7.4 Hz, 1H, ArH), 7.02(d, J=7.2 Hz, 1H, ArH), 7.39˜7.50 (m, 2H, ArH), 7.62˜7.64 (m, 2H, ArH),8.20˜8.23 (m, 1H, ArH), 8.39˜8.40 (m, 1H, ArH).

<Example 254>N-(1-Amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-4-chloronicotinamide

Fe (24 mg, 0.44 mmol) and 2 drops of conc. HCl were sequentially addedto a solution of4-chloro-N-(4b-hydroxy-7-isopropyl-1-nitro-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)nicotinamide(70 mg, 0.15 mmol) in an ethanol:H₂O (20 ml:2 ml) solvent and heated for2 hrs under reflux. After vacuum concentration, purification by columnchromatography (10% MeOH in CH₂Cl) afforded the title compound as ayellow solid (50 mg, 74%).

¹H-NMR (300 MHz, CD₃OD) δ 1.18 (d, J=6.8 Hz, 6H, CH₃), 2.83 (sep, J=6.8Hz, 1H, CH), 6.56 (d, J=7.2 Hz, 1H, ArH), 6.66˜6.68 (m, 2H, ArH), 6.86(d, J=7.7 Hz, 1H, ArH), 7.00 (d, J=7.1 Hz, 1H, ArH), 7.40˜7.46 (m, 2H,ArH), 7.77 (d, J=7.1 Hz, 1H, ArH), 8.40 (s, 1H, ArH).

<Example 255>N-(1-Amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-5-fluoronicotinamide

Fe (72 mg, 1.29 mmol) and 2 drops of conc. HCl were sequentially addedto a solution of5-fluoro-N-(4b-hydroxy-7-isopropyl-1-nitro-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)nicotinamide(200 mg, 0.43 mmol) in an ethanol:H₂O (20 ml:2 ml) solvent, and heatedfor 4 hrs under reflux. After vacuum concentration, purification bycolumn chromatography (EtOAc:hexane=2:1) afforded the title compound asa yellow solid (50 mg, 27%).

¹H-NMR (300 MHz, CD₃OD) δ 1.18 (d, J=6.8 Hz, 6H, CH₃), 2.84 (sep, J=6.8Hz, 1H, CH), 6.67˜6.71 (m, 2H, ArH), 6.88 (d, J=7.9 Hz, 1H, ArH), 7.01(d, J=7.3 Hz, 1H, ArH), 7.42˜7.45 (m, 2H, ArH), 8.03 (d, J=8.7 Hz, 1H,ArH), 8.60 (s, 1H, ArH), 8.86 (s, 1H, ArH).

<Example 256>N-(1-Amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-5-hydroxynicotinamide

A solution of5-hydroxy-N-(4b-hydroxy-7-isopropyl-1-nitro-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)nicotinamide(50 mg, 0.11 mmol) in methanol (5 ml) was mixed with 20 wt % ammoniumsulfide (0.2 ml), and heated for 3.5 hrs under reflux. After removal ofthe solvent, the reaction mixture was extracted with CH₂Cl₂, dehydratedwith Na₂SO₄, filtered, and concentrated. Purification by columnchromatography (3% MeOH in CH₂Cl₂) afforded the title compound as ayellow solid (168 mg, 40%).

¹H-NMR (300 MHz, CD₃OD) δ 1.18 (d, J=6.8 Hz, 6H, CH₃), 2.84 (sep, J=6.8Hz, 1H, CH), 6.66˜6.71 (m, 2H, ArH), 6.88 (d, J=7.9 Hz, 1H, ArH), 7.00(d, J=7.5 Hz, 1H, ArH), 8.05 (br, 1H, ArH), 8.24 (br, 1H, ArH).

<Example 257>N-(1-Amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-3-hydroxypicolinamide

A solution of3-hydroxy-N-(4b-hydroxy-7-isopropyl-1-nitro-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)picolinamide(190 mg, 0.41 mmol) in methanol (5 ml) was mixed with 20 wt % ammoniumsulfide (0.2 ml), and heated for 2 hrs under reflux. After removal ofthe solvent, the reaction mixture was extracted with CH₂Cl₂, dehydratedwith Na₂SO₄, filtered, and concentrated. Purification by columnchromatography (EtOAc:hexane=1:1) afforded the title compound as ayellow solid (47 mg, 27%).

¹H-NMR (300 MHz, CD₃OD) δ 1.16 (d, J=6.9 Hz, 6H, CH₃), 2.79 (sep, J=6.9Hz, 1H, CH), 6.50˜6.74 (m, 2H, ArH), 6.80 (d, J=7.8 Hz, 1H, ArH),7.00˜7.02 (m, 1H, ArH), 7.33˜7.55 (m, 2H, ArH).

<Example 258>N-(1-Amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-4-methylnicotinamide

Fe powder (0.17 g, 3.17 mmol), conc. HCl (0.01 ml), and water (1 ml)were added in that order to a solution ofN-(4b-hydroxy-7-isopropyl-1-nitro-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-4-methylnicotinamide(0.20 g, 0.43 mmol) in absolute ethanol (10 ml), and heated for 2 hrsunder reflux. The reaction mixture was washed with ethylacetate, andfiltered to remove Fe powder. The filtrate was alkalified with NaHCO₃,and washed many times with water. The organic layer was dried andfiltered, followed by purification for 30 min by column chromatography(ethylacetate:hexane=1:4) packed with Et₃N-treated silica gel to affordthe title compound. 0.11 g (53%).

¹H-NMR (300 MHz, CD₃OD) δ 1.17 (d, J=6.9 Hz, 6H, CH₃) 2.49 (s, 3H, CH₃)2.77-2.87 (sept, 1H, CH) 6.66-6.80 (m, 2H, ArH) 6.85 (d, J=7.5 Hz, 1H,ArH) 7.04 (d, J=6.9 Hz, 1H, ArH) 7.32 (d, J=5.1 Hz, 1H, ArH) 7.44-7.49(m, 2H, ArH) 8.41 (d, J=5.4 Hz, 1H, ArH) 8.63 (s, 1H, ArH).

<Example 259>N-(1-Amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-5-methylnicotinamide

Fe powder (0.23 g, 4.28 mmol), conc. HCl (0.04 ml), and water (1 ml)were added in that order to a solution ofN-(4b-hydroxy-7-isopropyl-1-nitro-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-5-methylnicotinamide(0.27 g, 0.58 mmol) in absolute ethanol (10 ml), and heated for 2 hrsunder reflux. The reaction mixture was washed with ethylacetate, andfiltered to remove Fe powder. The filtrate was alkalified with NaHCO₃,and washed many times with water. The organic layer was dried andfiltered, followed by purification for 30 min by column chromatography(ethylacetate:hexane=1:4) packed with Et₃N-treated silica gel to affordthe title compound. 0.13 g (52%).

¹H-NMR (300 MHz, CD₃OD) δ 1.17 (d, J=6.9 Hz, 6H, CH₃) 2.37 (s, 3H, CH₃)2.78-2.87 (sept, 1H, CH) 6.67-6.74 (m, 2H, ArH) 6.86 (d, J=7.8 Hz, 1H,ArH) 7.03 (d, J=7.2 Hz, 1H, ArH) 7.40-7.48 (m, 2H, ArH) 8.07 (s, 1H,ArH) 8.49 (s, 1H, ArH) 8.79 (s, 1H, ArH).

<Example 260>N-(1-Amino-4b-hydroxy-7,8-dimethyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)nicotinamide

Fe powder (0.15 g, 2.70 mmol), conc. HCl (0.04 ml) and water (1 ml) wereadded in that order to a solution ofN-(4b-hydroxy-7,8-dimethyl-1-nitro-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)nicotinamide(0.15 g, 0.34 mmol) in absolute ethanol (10 ml), and heated for 2 hrsunder reflux.

The reaction mixture was washed with ethylacetate, and filtered toremove Fe powder. The filtrate was alkalified with NaHCO₃, and washedmany times with water. The organic layer was dried and filtered,followed by purification for 30 min by column chromatography(ethylacetate:hexane=2:1) packed with Et₃N-treated silica gel to affordthe title compound. 70 mg (50%).

¹H-NMR (300 MHz, CD₃OD) δ 1.17 (d, J=6.9 Hz, 6H, CH₃) 2.56 (s, 3H, CH₃)6.67-6.70 (m, 2H, ArH) 6.87 (d, J=6.9 Hz, 1H, ArH) 7.01 (d, J=6.3 Hz,1H, ArH) 7.42-7.44 (m, 2H, ArH) 7.58 (d, J=5.1 Hz, 1H, ArH) 7.67 (s, 1H,ArH) 8.49 (d, J=5.1 Hz, 1H, ArH).

<Example 261>N-(1-Amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-5-methoxynicotinamide

Fe powder (0.12 g, 2.30 mmol), conc. HCl (0.03 ml), and water (1 ml)were added in that order to a solution ofN-(4b-hydroxy-7-isopropyl-1-nitro-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-5-methoxynicotinamide(0.15 g, 0.31 mmol) in absolute ethanol (10 ml), and heated for 2 hrsunder reflux. The reaction mixture was washed with ethylacetate, andfiltered to remove Fe powder. The filtrate was alkalified with NaHCO₃,and washed many times with water. The organic layer was dried andfiltered, followed by purification for 30 min by column chromatography(ethylacetate:hexane=1:1) packed with Et₃N-treated silica gel to affordthe title compound. 80 mg (57%).

¹H-NMR (300 MHz, CD₃OD) δ 1.18 (d, J=6.6 Hz, 6H, CH₃) 2.81-2.86 (sept,1H, CH) 3.89 (s, 3H, OMe) 6.67-6.70 (m, 2H, ArH) 6.88 (d, J=7.2 Hz, 1H,ArH) 7.01 (d, J=6.6 Hz, 1H, ArH) 7.43-7.45 (m, 2H, ArH) 7.82 (s, 1H,ArH) 8.34 (s, 1H, ArH) 8.58 (s, 1H, ArH).

<Example 262>N-(1-Amino-4b-hydroxy-7,8-dimethyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)quinoline-6-carboxamide

Fe powder (0.16 g, 3.03 mmol), conc. HCl (0.04 ml), and water (1 ml)were added in that order to a solution ofN-(4b-hydroxy-7,8-dimethyl-1-nitro-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)quinoline-6-carboxamide(0.20 g, 0.41 mmol) in absolute ethanol (10 ml), and heated for 2 hrsunder reflux. The reaction mixture was washed with ethylacetate, andfiltered to remove Fe powder. The filtrate was alkalified with NaHCO₃,and washed many times with water. The organic layer was dried andfiltered, followed by purification for 30 min by column chromatography(ethylacetate:hexane=2:1) packed with Et₃N-treated silica gel to affordthe title compound. 0.16 g (86%).

¹H-NMR (300 MHz, CD₃OD) δ 2.22 (d, J=8.4 Hz, 6H, CH₃) 6.61 (s, 1H, ArH)6.70 (d, J=8.1 Hz, 1H, ArH) 7.01 (d, J=6.6 Hz, 1H, ArH) 7.34 (s, 1H,ArH) 7.46-7.48 (m, 1H, ArH) 7.78-7.79 (m, 1H, ArH) 8.10-8.14 (m, 1H,ArH) 8.20-8.28 (m, 1H, ArH) 8.62 (s, 1H, ArH) 8.74 (d, J=6.9 Hz, 1H,ArH).

<Example 263>N-(1-Amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-ylquinoline-2-carboxamide

Fe (135 mg, 2.42 mmol and 2 drops of conc. HCl were sequentially addedto a solution ofN-(4b-hydroxy-7-isopropyl-1-nitro-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-ylquinoline-2-carboxamide(400 mg, 0.81 mmol in an ethanol:H₂O (20 ml:2 ml solvent and heated for1.5 hrs under reflux. After vacuum concentration, purification by columnchromatography (EtOAc:hexane=1:2) afforded the title compound as ayellow solid (132 mg, 35%).

¹H-NMR (300 MHz, CD₃OD) δ 1.21 (d, J=6.8 Hz, 6H, CH₃), 2.87 (sep, J=6.8Hz, 1H, CH), 6.70˜6.73 (m, 2H, ArH), 6.92 (d, J=7.9 Hz, 1H, ArH), 7.03(d, J=7.3 Hz, 1H, ArH), 7.44˜7.51 (m, 2H, ArH), 7.66 (t, J=7.6 Hz, 1H,ArH), 7.80 (t, J=7.3 Hz, 1H, ArH), 7.97 (d, J=8.1 Hz, 1H, ArH),8.07˜8.13 (m, 2H, ArH), 8.44 (d, J=8.4 Hz, 1H, ArH).

<Example 264>N-(1-Amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl-3-bromobenzo[b]thiophene-2-carboxamide

Fe (87 mg, 1.56 mmol and 2 drops of conc. HCl were sequentially added toa solution of3-bromo-N-(4b-hydroxy-7-isopropyl-1-nitro-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)benzo[b]thiophene-2-carboxamide(250 mg, 0.52 mmol in an ethanol:H₂O (20 ml:2 ml solvent and heated for2 hrs under reflux. After vacuum concentration, purification by columnchromatography (EtOAc:hexane=1:4) afforded the title compound as ayellow solid (130 mg, 46%).

¹H-NMR (300 MHz, CD₃OD) δ 1.19 (d, J=6.9 Hz, 6H, CH₃), 2.85 (sep, J=6.9Hz, 1H, CH), 6.66˜6.80 (m, 2H, ArH), 6.89˜6.92 (m, 1H, ArH), 7.01˜7.05(m, 1H, ArH), 7.46˜7.55 (m, 4H, ArH), 7.88˜7.93 (m, 2H, ArH).

<Example 265>N-(1-Amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl-1H-indole-2-carboxamide

Fe (35 mg, 0.62 mmol and 2 drops of con. HCl were sequentially added toa solution ofN-(4b-hydroxy-7-isopropyl-1-nitro-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)-1H-indole-2-carboxamide(100 mg, 0.21 mmol) in an ethanol:H₂O (15 ml:1 ml) solvent and heatedfor 4 hrs under reflux. After vacuum concentration, purification bycolumn chromatography (EtOAc:hexane=1:3) afforded the title compound asa yellow solid (80 mg, 84%).

¹H-NMR (300 MHz, CD₃OD) δ 1.19 (d, J=6.8 Hz, 6H, CH₃), 2.84 (sep, J=6.8Hz, 1H, CH), 6.69˜6.80 (m, 2H, ArH), 6.88 (d, J=8.1 Hz, 1H, ArH),7.02˜7.07 (m, 2H, ArH), 7.18˜7.23 (m, 2H, ArH), 7.37˜7.50 (m, 3H, ArH),7.59 (d, J=8.0 Hz, 1H, ArH).

<Example 266>N-(1-Amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)isoquinoline-1-carboxamide

Fe (68 mg, 1.21 mmol) and 2 drops of conc. HCl were sequentially addedto a solution ofN-(4b-hydroxy-7-isopropyl-1-nitro-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)isoquinoline-1-carboxamide(200 mg, 0.40 mmol) in an ethanol:H₂O (20 ml:2 ml) solvent and heatedfor 3.5 hrs under reflux. After vacuum concentration, purification bycolumn chromatography (EtOAc:hexane=1:4) afforded the title compound asa yellow solid (155 mg, 81%).

¹H-NMR (300 MHz, CD₃OD) δ 1.14 (dd, J=6.9 Hz, 1.5 Hz, 6H, CH₃), 2.80(sep, J=6.9 Hz, 1H, CH), 6.67 (s, 1H, ArH), 6.70 (d, J=8.3 Hz, 1H, ArH),6.85 (dd, J=8.0 Hz, 1.0 Hz, 1H, ArH), 7.05 (d, J=7.1 Hz, 1H, ArH),7.43˜7.50 (m, 2H, ArH), 7.64 (t, J=7.5 Hz, 1H, ArH), 7.73 (t, J=8.0 Hz,1H, ArH), 7.87˜7.92 (m, 2H, ArH), 8.44 (d, J=5.6 Hz, 1H, ArH), 8.94 (d,J=8.4 Hz, 1H, ArH).

<Example 267>N-(1-Amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-6-fluoro-4-methoxyquinoline-3-carboxamide

Fe powder (46.2 mg, 0.82 mmoles) and 5 drops of conc. HCl weresequentially added to a solution of6-fluoro-N-(4b-hydroxy-7-isopropyl-1-nitro-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)-4-methoxyquinoline-3-carboxamide(0.15 g, 0.28 mmoles) in an ethanol:water (10:1, 10 mL:1 mL) solvent,and heated for 3 hrs under reflux. The reaction mixture was washed withethylacetate, and hot filtered to remove Fe powder. The filtrate wasextracted ethylacetate and water, followed by separation andpurification by column chromatography to afford the title compound. 15mg (11%).

¹H-NMR (300 MHz, CD₃OD): δ 1.21 (d, J=6.9 Hz, 6H, CH₃) 2.87 (sept, J=6.9Hz, 1H, CH) 3.85 (s, 3H, OCH₃) 6.69 (s, 2H, ArH) 6.82 (d, J=7.2 Hz, 1H,ArH) 6.90 (d, J=7.8 Hz, 1H, ArH) 7.44-7.46 (m, 2H, ArH) 7.56 (br, 1H,ArH) 7.66 (br, 1H, ArH) 8.0 (m, 1H, ArH) 8.67 (s, 1H, ArH).

<Example 268>N-(1-Amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-1-methyl-1H-indole-2-carboxamide

Fe powder (0.12 g, 2.20 mmol), conc.HCl (0.03 ml), and water (1 ml) wereadded in that order to a solution ofN-(4b-hydroxy-7-isopropyl-1-nitro-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)-1-methyl-1H-indole-2-carboxamide(0.15 g, 0.31 mmol) in absolute ethanol (10 ml), and heated for 2 hrsunder reflux. The reaction mixture was washed with ethylacetate, and hotfiltered to remove Fe powder. The filtrate was alkalified with NaHCO₃,and washed many times with water. The organic layer was dried andfiltered, followed by purification for 30 min by column chromatography(ethylacetate:hexane=1:2) packed with Et₃N-treated silica gel to affordthe title compound. 50 mg (35%).

¹H-NMR (300 MHz, CD₃OD) δ 1.18 (d, J=6.9 Hz, 6H, CH₃) 2.82-2.86 (sept,1H, CH) 3.89 (s, 3H, CH₃) 6.68 (s, 1H, ArH) 6.87-6.88 (m, 1H, ArH)7.03-7.13 (m, 2H, ArH) 7.18 (s, 1H, ArH) 7.24-7.29 (m, 2H, ArH)7.39-7.47 (m, 3H, ArH) 7.60 (d, J=7.8 Hz, 1H, ArH).

<Example 269>N-(1-Amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-3-chloro-6-fluorobenzo[b]thiophene-2-carboxamide

Fe powder (0.05 g, 1.05 mmol), conc.HCl (0.02 ml), and water (0.5 ml)were added in that order to a solution of3-chloro-6-fluoro-N-(4b-hydroxy-7-isopropyl-1-nitro-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)benzo[b]thiophene-2-carboxamide(80 mg, 0.14 mmol) in an absolute ethanol (5 ml), and heated for 2 hrsunder reflux. The reaction mixture was washed with ethylacetate, and hotfiltered to remove Fe powder. The filtrate was alkalified with NaHCO₃,and washed many times with water. The organic layer was dried andfiltered, followed by purification for 30 min by column chromatography(ethylacetate:hexane=1:4) packed with Et₃N-treated silica gel to affordthe title compound. 50 mg (68%).

¹H-NMR (300 MHz, CD₃OD) δ 1.15 (d, J=6.6 Hz, 6H, CH₃) 2.76-2.85 (sept,1H, CH) 6.69 (s, 1H, ArH) 6.75 (d, J=6.6 Hz, 1H, ArH) 6.84 (d, J=7.5 Hz,1H, ArH) 7.03 (d, J=7.2 Hz, 1H, ArH) 7.28 (t, J=7.2 Hz, 1H, ArH)7.43-7.48 (m, 2H, ArH) 7.66 (d, J=8.7 Hz, 1H, ArH) 7.83-7.88 (m, 1H,ArH).

<Example 270>N-(1-Amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-3-chloro-6-methylbenzo[b]thiophene-2-carboxamide

Fe powder (0.11 g, 1.97 mmol), conc. HCl (0.05 ml), and water (1 ml)were added in that order to a solution of3-chloro-N-(4b-hydroxy-7-isopropyl-1-nitro-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)-6-methylbenzo[b]thiophene-2-carboxamide(0.15 g, 0.27 mmol) in absolute ethanol (10 ml), and heated for 2 hrsunder reflux. The reaction mixture was washed with ethylacetate, andfiltered to remove Fe powder. The filtrate was alkalified with NaHCO₃,and washed many times with water. The organic layer was dried andfiltered, followed by purification for 30 min by column chromatography(ethylacetate:hexane=1:4) packed with Et₃N-treated silica gel to affordthe title compound. 21 mg (15%).

¹H-NMR (300 MHz, CD₃OD) δ 1.16-1.18 (m, 6H, CH₃) 2.45 (s, 3H, CH₃)2.80-2.86 (sept, 1H, CH) 6.70 (s, 1H, ArH) 6.72-6.80 (m, 1H, ArH)6.84-6.95 (m, 1H, ArH) 7.00-7.05 (m, 1H, ArH) 7.33 (d, J=8.1 Hz, 1H,ArH) 7.37-7.52 (m, 2H, ArH) 7.66 (s, 1H, ArH) 7.75 (d, J=8.1 Hz, 1H,ArH).

<Example 271>N-(1-Amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-1,3-dimethyl-1H-pyrazolo[3,4-b]pyridine-5-carboxamide

Fe powder (137 mg, 2.45 mmol), conc. HCl (0.02 ml), and water (1 mL)were added in that order to a solution ofN-(4b-hydroxy-7-isopropyl-1-nitro-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-1,3-dimethyl-1H-pyrazolo[3,4-b]pyridine-5-carboxamide(180 mg, 0.35 mmol) in absolute ethanol (10 mL), and heated for 3 hrsunder reflux. The reaction mixture was washed with ethylacetate, and hotfiltered to remove Fe powder. The filtrate was alkalified with NaHCO₃,and washed many times with water. The organic layer was dried andfiltered, followed by purification by column chromatography(ethylacetate:hexane=1:1) packed with Et₃N-treated silica gel to affordthe title compound (25 mg, 16%).

¹H-NMR (300 MHz, CD₃OD) δ 1.15 (d, J=6.9 Hz, 6H), 2.54 (s, 3H),2.80-2.89 (m, 1H), 4.03 (s, 3H), 6.68-6.71 (m, 2H), 6.88 (d, J=7.6 Hz,1H), 7.02 (d, J=7.3 Hz, 1H), 7.42-7.50 (m, 2H), 8.71 (s, 1H), 8.94 (s,1H).

<Example 272>N-(1-Amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)imidazo[1,2-a]pyridine-6-carboxamide

Fe (80 mg, 1.42 mmol) and 2 drops of conc. HCl were sequentially addedto a solution ofN-(4b-hydroxy-7-isopropyl-1-nitro-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)imidazo[1,2-a]pyridine-6-carboxamide(230 mg, 0.47 mmol) in an ethanol:H₂O (10 ml:1 ml) solvent, and heatedfor 4.5 hrs under reflux. After vacuum concentration, purification bycolumn chromatography (5% methanol in methylene chloride) afforded thetitle compound as a brown solid (50 mg, 23%).

¹H-NMR (300 MHz, CD₃OD) δ 1.03-1.42 (m, 6H), 3.05-3.30 (m, 1H),6.61-6.75 (m, 2H), 6.81-6.92 (m, 1H), 6.96-7.05 (m, 1H), 7.31-8.32 (m,6H), 9.05-9.30 (m, 1H).

<Example 273>N-(1-Amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)pyrazolo[1,5-a]pyrimidine-2-carboxamide

Fe (97 mg, 1.73 mmol) and 2 drops of conc. HCl were sequentially addedto a solution ofN-(4b-hydroxy-7-isopropyl-1-nitro-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)pyrazolo[1,5-a]pyrimidine-2-carboxamide(280 mg, 0.58 mmol) in an ethanol:H₂O (20 ml:2 ml) solvent, and heatedfor 3.5 hrs under reflux. After vacuum concentration, purification bycolumn chromatography (EtOAc:hexane=2:1) afforded the title compound asa yellow solid (80 mg, 30%).

¹H-NMR (300 MHz, CD₃OD) δ 1.17 (d, J=6.8 Hz, 6H, CH₃), 2.81 (sep, J=6.8Hz, 1H, CH), 6.63˜6.72 (m, 2H, ArH), 6.83˜6.87 (m, 1H, ArH), 7.00˜7.12(m, 3H, ArH), 7.43˜7.51 (m, 2H, ArH), 8.55˜8.57 (m, 1H, ArH), 8.96 (d,J=7.3 Hz, 1H, ArH).

<Example 274>N-(1-Amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-3-methylbenzo[b]thiophene-2-carboxamide

Fe powder (0.04 g, 0.85 mmol), conc. HCl (0.03 ml), and water (0.5 ml)were added in that order to a solution ofN-(4b-hydroxy-7-isopropyl-1-nitro-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-3-methylbenzo[b]thiophene-2-carboxamide(60 mg, 0.11 mmol) in absolute ethanol (5 ml), and heated for 2 hrsunder reflux. The reaction mixture was washed with ethylacetate, and hotfiltered to remove Fe powder. The filtrate was alkalified with NaHCO₃,and washed many times with water. The organic layer was dried andfiltered, followed by purification for 30 min by column chromatography(ethylacetate:hexane=1:4) packed with Et₃N-treated silica gel to affordthe title compound. 30 mg (53%).

¹H-NMR (300 MHz, CD₃OD) δ 1.00-1.27 (m, 6H), 2.53-2.64 (m, 3H),2.70-2.84 (m, 1H), 6.54-6.87 (m, 3H), 6.96-7.10 (m, 1H), 7.25-7.52 (m,4H), 7.69-7.86 (m, 2H).

<Example 275>N-(1-Amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)quinoxaline-2-carboxamide

Fe powder (0.16 g, 2.92 mmol), conc. HCl (0.03 ml) and water (1 ml) wereadded in that order to a solution ofN-(4b-hydroxy-7-isopropyl-1-nitro-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)quinoxaline-2-carboxamide(0.20 g, 0.40 mmol) in absolute ethanol (10 ml), and heated for 2 hrsunder reflux. The reaction mixture was washed with ethylacetate, and hotfiltered to remove Fe powder. The filtrate was alkalified with NaHCO₃,and washed many times with water. The organic layer was dried andfiltered, followed by purification for 30 min by column chromatography(ethylacetate:hexane=1:2) packed with Et₃N-treated silica gel to affordthe title compound. 68 mg (37%).

¹H-NMR (300 MHz, CD₃OD) δ 1.21 (d, J=6.9 Hz, 6H, CH₃) 2.82-2.91 (sept,1H, CH) 6.71 (s, 1H, ArH) 6.91 (d, J=7.5 Hz, 1H, ArH) 7.04 (d, J=7.2 Hz,1H, ArH) 7.47-7.49 (m, 2H, ArH) 7.90-7.98 (m, 3H, ArH) 8.15-8.28 (m, 2H,ArH) 9.40 (s, 1H, ArH).

<Example 276>N-(1-Amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)pyridazine-4-carboxamide

Fe powder (0.03 g, 0.55 mmol), conc. HCl (0.01 ml), and water (0.5 ml)were added in that order to a solution ofN-(4b-hydroxy-7-isopropyl-1-nitro-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)pyridazine-4-carboxamide(50 mg, 0.11 mmol) in absolute ethanol (5 ml), and heated for 2 hrsunder reflux. The reaction mixture was washed with ethylacetate, and hotfiltered to remove Fe powder. The filtrate was alkalified with NaHCO₃,and washed many times with water. The organic layer was dried andfiltered, followed by purification for 30 min by column chromatography(ethylacetate:hexane=1:2) packed with Et₃N-treated silica gel to affordthe title compound. 26 mg (56%).

¹H-NMR (300 MHz, CD₃OD) δ 1.17 (d, J=6.7 Hz, 6H, CH₃) 2.78-2.87 (sept,1H, CH) 6.68-6.74 (m, 2H, ArH) 6.87 (d, J=7.5 Hz, 1H, ArH) 7.02 (d,J=7.2 Hz, 1H, ArH) 7.40-7.48 (m, 2H, ArH) 8.04 (s, 2H, ArH) 9.32 (d,J=5.0 Hz, 1H, ArH) 9.51 (s, 1H, ArH).

<Example 277>N-(1-Amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)quinoxaline-6-carboxamide

Fe powder (0.028 g, 0.50 mmol), conc. HCl (0.01 ml) and water (0.5 ml)were added in that order to a solution ofN-(4b-hydroxy-7-isopropyl-1-nitro-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)quinoxaline-6-carboxamide(50 mg, 0.11 mmol) in absolute ethanol (5 ml), and heated for 2 hrsunder reflux. The reaction mixture was washed with ethylacetate, and hotfiltered to remove Fe powder. The filtrate was alkalified with NaHCO₃,and washed many times with water. The organic layer was dried andfiltered, followed by purification for 30 min by column chromatography(ethylacetate 100%) packed with Et₃N-treated silica gel to afford thetitle compound. 38 mg (81%).

¹H-NMR (300 MHz, CD₃OD) δ 1.19 (d, J=6.8 Hz, 6H, CH₃) 2.83-2.89 (sept,1H, CH) 6.75 (s, 1H, ArH) 6.96d, J=7.8 Hz, 1H, ArH) 7.47-7.54 (m, 3H,ArH) 8.08-8.24 (m, 3H, ArH) 8.63 (s, 1H, ArH) 8.93 (s, 1H, ArH).

<Example 278>N-(1-Amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)tetrazolo[1,5-a]pyridine-6-carboxamide

Fe (121 mg, 2.16 mmol) and 4 drops of conc. HCl were sequentially addedto a solution ofN-(4b-hydroxy-7-isopropyl-1-nitro-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)tetrazolo[1,5-a]pyridine-6-carboxamide(350 mg, 0.72 mmol) in an ethanol:H₂O (15 ml:1.5 ml) solvent, and heatedfor 2.5 hrs under reflux. After vacuum concentration, purification bycolumn chromatography (EtOAc:hexane=2:1) afforded the title compound asa yellow solid (269 mg, 80%).

¹H-NMR (300 MHz, CD₃OD) δ 1.18 (d, J=6.9 Hz, 6H, CH₃), 2.85 (sep, J=6.9Hz, 1H, CH), 6.69˜6.71 (m, 2H, ArH), 6.90 (d, J=7.7 Hz, 1H, ArH), 7.02(d, J=7.2 Hz, 1H, ArH), 7.43˜7.46 (m, 2H, ArH), 8.07˜8.18 (m, 2H, ArH),9.65 (s, 1H, ArH).

<Example 279>N-(1-Amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)tetrazolo[1,5-a]pyridine-8-carboxamide

Fe (55 mg, 0.99 mmol) and 3 drops of conc. HCl were sequentially addedto a solution ofN-(4b-hydroxy-7-isopropyl-1-nitro-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)tetrazolo[1,5-a]pyridine-8-carboxamide(160 mg, 0.33 mmol) in an ethanol:H₂O (15 ml:1.5 ml), and heated for 2hrs under reflux. After vacuum concentration, purification by columnchromatography (EtOAc:hexane=2:1) afforded the title compound as ayellow solid (117 mg, 76%).

¹H-NMR (300 MHz, CD₃OD) δ 1.23 (d, J=6.9 Hz, 6H, CH₃), 2.89 (sep, J=6.9Hz, CH), 6.70˜6.74 (m, 2H, ArH), 6.95 (d, J=7.8 Hz, 1H, ArH), 7.02 (d,J=8.0 Hz, 1H, ArH), 7.44˜7.55 (m, 3H, ArH), 8.41 (d, J=7.3 Hz, 1H, ArH),9.29 (d, J=7.3 Hz, 1H, ArH).

<Example 280>N-(1-Amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-7-methylimidazo[1,2-a]pyridine-2-carboxamide

Fe powder (0.27 g, 4.91 mmol), conc. HCl (0.04 ml) and water (1 ml) wereadded in that order to a solution ofN-(4b-hydroxy-7-isopropyl-1-nitro-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)quinoxaline-6-carboxamide(0.49 g, 0.98 mmol) in absolute ethanol (10 ml). The reaction mixturewas washed with ethylacetate, and hot filtered to remove Fe powder. Thefiltrate was alkalified with NaHCO₃, and washed many times with water.The organic layer was dried and filtered, followed by purification for30 min by column chromatography (ethylacetate:hexane=1:1) packed withEt₃N-treated silica gel to afford the title compound. 80 mg (17%).

¹H-NMR (300 MHz, CDCl₃) δ 0.62-1.84 (m, 6H), 2.90-3.00 (m, 1H),6.43-6.84 (m, 8H), 6.98-7.58 (m, 3H), 7.72-8.17 (m, 3H).

<Example 281>N-(1-Amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-7-methyl-[1,2,4]triazolo[1,5-a]pyrimidine-2-carboxamide

Fe powder (0.23 g, 4.22 mmol), conc. HCl (0.04 ml), and water (1 ml)were added in that order to a solution ofN-(4b-hydroxy-7-isopropyl-1-nitro-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-7-methyl-[1,2,4]triazolo[1,5-a]pyrimidine-2-carboxamide(0.29 g, 0.57 mmol) in absolute ethanol (10 ml), and heated for 2 hrsunder reflux. The reaction mixture was washed with ethylacetate, and hotfiltered to remove Fe powder. The filtrate was alkalified with NaHCO₃,and washed many times with water. The organic layer was dried andfiltered, followed by purification for 30 min by column chromatography(ethylacetate 100%) packed with Et₃N-treated silica gel to afford thetitle compound. 0.17 g (62%).

¹H-NMR (300 MHz, CD₃OD) δ 1.19 (d, J=6.9 Hz, 6H, CH₃) 2.82-2.85 (m, 4H,CH, CH₃) 6.67-6.74 (m, 2H, ArH) 6.87-6.94 (m, 1H, ArH) 7.00-7.04 (m, 1H,ArH) 7.30 (d, J=4.7 Hz, 1H, ArH) 7.44-7.51 (m, 2H, ArH) 8.81 (d, J=4.6Hz, 1H, ArH).

<Example 282>N-(1-Amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-5,7-dimethylpyrazolo[1,5-a]pyrimidine-3-carboxamide

Fe powder (0.06 g, 1.16 mmol), conc. HCl (0.04 ml), and water (0.5 ml)were added in that order to a solution ofN-(4b-hydroxy-7-isopropyl-1-nitro-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-5,7-dimethylpyrazolo[1,5-a]pyrimidine-3-carboxamide(0.12 g, 0.23 mmol) in absolute ethanol (5 ml), and heated for 2 hrsunder reflux. The reaction mixture was washed with ethylacetate, and hotfiltered to remove Fe powder. The filtrate was alkalified with NaHCO₃,and washed many times with water. The organic layer was dried andfiltered, followed by purification for 30 min by column chromatography(ethylacetate 100%) packed with Et₃N-treated silica gel to afford thetitle compound. 60 mg (54%).

¹H-NMR (300 MHz, CD₃OD) δ 1.20 (dd, J=6.9, 2.3 Hz, 6H, CH₃) 2.53 (s, 3H,CH₃) 2.76 (s, 3H, CH₃) 2.84-2.88 (m, 1H, CH) 6.71-6.80 (m, 2H, ArH) 6.90(d, J=7.8 Hz, 1H, ArH) 6.99 (s, 1H, ArH) 7.04 (d, J=7.4 Hz, 1H, ArH)7.42-7.51 (m, 2H, ArH) 8.39 (s, 1H, ArH).

<Example 283>N-(1-Amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)indolizine-2-carboxamide

Fe powder (76 mg, 1.37 mmol), conc. HCl (0.02 ml, and water (1.5 mL)were added in that order to a solution ofN-(4b-hydroxy-7-isopropyl-4-nitro-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)indolizine-2-carboxamide(220 mg, 0.46 mmol) in absolute ethanol (15 mL), and heated for 3 hrsunder reflux. The reaction mixture was washed with ethylacetate, and hotfiltered to remove Fe powder. The filtrate was alkalified with NaHCO₃,and washed many times with water. The organic layer was dried andfiltered, followed by purification for 30 min by column chromatography(ethylacetate:hexane=1:1) packed with Et₃N-treated silica gel to affordthe title compound as a yellow solid (43 mg, 21%).

¹H-NMR (300 MHz, CD₃OD) δ 1.18 (d, J=6.8 Hz, 6H), 2.84 (sept, J=6.8 Hz,1H), 6.50-6.56 (m, 2H), 6.65-6.72 (m, 3H), 6.79 (s, 1H), 6.88 (d, J=7.8Hz, 1H), 7.01 (d, J=7.4 Hz, 1H), 7.33 (d, J=9.2 Hz, 1H), 7.44-7.48 (m,1H), 7.87 (s, 1H), 8.02 (d, J=7.0 Hz, 1H).

<Example 284>N-(1-Amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-1,6-diisopropyl-1H-pyrazolo[3,4-b]pyridine-4-carboxamide

Fe powder (78 mg, 1.39 mmol), conc. HCl (0.02 ml), and water (1.5 mL)were added in that order to a solution ofN-(4b-hydroxy-7-isopropyl-4-nitro-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-1,6-diisopropyl-1H-pyrazolo[3,4-b]pyridine-4-carboxamide(264 mg, 0.46 mmol) in absolute ethanol (15 mL), and heated for 3 hrsunder reflux. The reaction mixture was washed with ethylacetate, and hotfiltered to remove Fe powder. The filtrate was alkalified with NaHCO₃,and washed many times with water. The organic layer was dried andfiltered, followed by purification by column chromatography(ethylacetate:hexane=1:1) packed with Et₃N-treated silica gel to affordthe title compound as a white solid (79.5 mg, 32%).

¹H-NMR (300 MHz, CD₃OD) δ 1.19 (d, J=6.6 Hz, 6H), 1.37 (d, J=6.8 Hz,6H), 1.54 (d, J=4.4 Hz, 6H), 2.75-2.90 (m, 1H), 3.17-3.30 (m, 1H),5.23-5.35 (m, 1H), 6.60-6.75 (m, 2H), 6.85-6.93 (m, 1H), 6.97-7.10 (m,1H), 7.40-7.53 (m, 1H), 7.57 (s, 1H), 8.23 (s, 1H).

<Example 285>N-(1-Amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)imidazo[1,2-a]pyrimidine-2-carboxamide

Fe powder (137 mg, 2.45 mmol), conc. HCl (0.02 ml), and water (1 mL)were added in that order to a solution ofN-(4b-hydroxy-7-isopropyl-4-nitro-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)imidazo[1,2-a]pyrimidine-2-carboxamide(110 mg, 0.23 mmol) in absolute ethanol (10 mL), and heated for 3 hrsunder reflux. The reaction mixture was washed with ethylacetate, and hotfiltered to remove Fe powder.

The filtrate was alkalified with NaHCO₃, and washed many times withwater. The organic layer was dried and filtered, followed bypurification by column chromatography (DCM:MeO=10:1) packed withEt₃N-treated silica gel to afford the title compound as a yellow solid(31 mg, 30%).

¹H-NMR (300 MHz, CDCl₃) δ 1.03-1.10 (m, 6H), 2.67-2.76 (m, 1H),5.57-5.62 (m, 1H), 6.40 (s, 1H), 6.63 (d, J=8.7 Hz, 1H), 6.74 (d, J=7.7Hz, 1H), 6.91-6.67 (m, 2H), 7.20 (d, J=7.5 Hz, 1H), 7.46-7.52 (m, 1H),7.56-7.64 (m, 1H), 7.95 (s, 1H), 8.34-8.39 (m, 1H), 8.63 (s, 1H).

<Example 286>N-(1-Amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-1-oxo-1,2-dihydroisoquinoline-3-carboxamide

Fe powder (47 mg, 0.83 mmol), conc. HCl (0.02 ml), and water (0.9 mL)were added in that order to a solution ofN-(4b-hydroxy-7-isopropyl-4-nitro-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-1-oxo-1,2-dihydroisoquinoline-3-carboxamide(142 mg, 0.28 mmol) in absolute ethanol (9 mL), and heated for 3 hrsunder reflux. The reaction mixture was washed with ethylacetate, and hotfiltered to remove Fe powder. The filtrate was alkalified with NaHCO₃,and washed many times with water. The organic layer was dried andfiltered, followed by purification for 30 min by column chromatography(EtOAc:hexane=2:1) packed with Et₃N-treated silica gel to afford thetitle compound as a yellow solid (58 mg, 43%).

¹H-NMR (300 MHz, CD₃OD) δ 1.19 (d, J=6.9 Hz, 6H), 2.84 (sept, J=6.9 Hz,1H), 6.69-6.74 (m, 2H), 6.89 (d, J=7.4 Hz, 1H), 7.02 (d, J=7.5 Hz, 1H),7.44-7.49 (m, 2H), 7.54 (s, 1H), 7.61-7.66 (m, 1H), 7.74-7.81 (m, 2H),8.31 (d, J=7.9 Hz, 1H).

<Example 287>N-(1-Amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)-3-methylimidazo[1,5-a]pyridine-1-carboxamide

Fe (77 mg, 1.38 mmol) and 4 drops of conc. HCl were sequentially addedto a solution ofN-(4b-hydroxy-7-isopropyl-1-nitro-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)-3-methylimidazo[1,5-a]pyridine-1-carboxamide(230 mg, 0.46 mmol) in an ethanol:H₂O (20 ml:2 ml) solvent, and heatedfor 2 hrs under reflux. After vacuum concentration, purification bycolumn chromatography (EtOAc:hexane=2:1) affordedN-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)-3-methylimidazo[1,5-a]pyridine-1-carboxamideas a yellow solid (90 mg, 42%).

¹H-NMR (300 MHz, CD₃OD) δ 1.19 (d, J=6.8 Hz, 6H, CH₃), 2.63 (s, 3H,CH₃), 2.85 (sep, J=6.8 Hz, 1H, CH), 6.67˜6.74 (m, 2H, ArH), 6.81˜6.89(m, 2H, ArH), 7.00˜7.09 (m, 2H, ArH), 7.42˜7.49 (m, 2H, ArH), 7.93˜7.96(m, 1H, ArH), 8.09 (d, J=7.4 Hz, 1H, ArH).

<Example 288>N-(1-Amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)-2H-indazole-3-carboxamide

Fe (35 mg, 0.62 mmol) and 3 drops of conc. HCl were sequentially addedto a solution ofN-(4b-hydroxy-7-isopropyl-1-nitro-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)-2H-indazole-3-carboxamide(100 mg, 0.21 mmol) in an ethanol:H₂O (10 ml:1 ml) solvent, and heatedfor 3 hrs under reflux. After vacuum concentration, purification bycolumn chromatography (EtOAc:hexane=1:1) afforded the title compoundN-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)-2H-indazole-3-carboxamideas a yellow solid (63 mg, 66%).

¹H-NMR (300 MHz, CD₃OD) δ 1.15 (d, J=6.9 Hz, 6H, CH₃), 2.80 (sep, J=6.9Hz, 1H, CH), 6.66˜6.72 (m, 2H, ArH), 6.86 (d, J=7.9 Hz, 1H, ArH), 7.04(d, J=7.3 Hz, 1H, ArH), 7.16˜7.21 (m, 1H, ArH), 7.34˜7.56 (m, 4H, ArH),8.09 (d, J=8.1 Hz, 1H, ArH).

<Example 289>N-(1-Amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-7-methylpyrazolo[1,5-a]pyrimidine-6-carboxamide

Fe powder (62 mg, 1.12 mmol), conc. HCl (0.02 ml) and water (1.2 mL)were added in that order to a solution ofN-(4b-hydroxy-7-isopropyl-4-nitro-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-7-methylpyrazolo[1,5-a]pyrimidine-6-carboxamide(186 mg, 0.37 mmol) in absolute ethanol (12 mL), and heated for 3 hrsunder reflux. The reaction mixture was washed with ethylacetate, and hotfiltered to remove Fe powder. The filtrate was alkalified with NaHCO₃,and washed many times with water. The organic layer was dried andfiltered, followed by purification by column chromatography(EA:hexane=1:1) packed with Et₃N-treated silica gel to afford the titlecompound as a yellow solid (125 mg, 72%).

¹H-NMR (300 MHz, CD₃OD) δ 1.17 (d, J=6.9 Hz, 6H), 2.83 (sept, J=7.1 Hz,1H), 2.97 (s, 3H), 6.68 (s, 1H), 6.70 (s, 1H), 6.71 (s, 1H), 6.87 (d,J=7.7 Hz, 1H), 7.06 (d, J=7.2 Hz, 1H), 7.34-7.51 (m, 2H), 8.25-8.26 (m,1H), 8.63 (s, 1H).

<Example 290>N-(1-Amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-1H-benzo[d]imidazole-2-carboxamide

Fe powder (54 mg, 0.96 mmol), conc. HCl (0.02 ml), and water (1.0 mL)were added in that order to a solution ofN-(4b-hydroxy-7-isopropyl-4-nitro-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-1H-benzo[d]imidazole-2-carboxamide(155 mg, 0.32 mmol) in absolute ethanol (10 mL) and heated for 3 hrsunder reflux. The reaction mixture was washed with ethylacetate, andfiltered to remove Fe powder. The filtrate was alkalified with NaHCO₃,and washed many times with water. The organic layer was dried andfiltered, followed by purification by column chromatography(EA:hexane=1:1) packed with Et₃N-treated silica gel to afford the titlecompound as a yellow solid (67 mg, 46%).

¹H-NMR (300 MHz, CD₃OD) δ 1.19 (d, J=6.9 Hz, 6H), 2.84 (sept, J=6.7 Hz,1H), 6.68 (s, 1H), 6.72 (s, 1H), 6.89 (d, J=7.4 Hz, 1H), 7.03 (d, J=7.3Hz, 1H), 7.32 (s, 1H), 7.34 (s, 1H), 7.44-7.50 (m, 2H), 7.55 (s, 1H),7.69 (s, 1H).

<Example 291>N-(1-Amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-5-fluoro-1H-benzo[d]imidazole-2-carboxamide

Fe powder (76 mg, 1.36 mmol), conc. HCl (0.02 ml), and water (1.5 mL)were added in that order to a solution of5-fluoro-N-(4b-hydroxy-7-isopropyl-4-nitro-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-1H-benzo[d]imidazole-2-carboxamide(227 mg, 0.45 mmol) in absolute ethanol (15 mL), and heated for 3 hrsunder reflux. The reaction mixture was washed with ethylacetate, and hotfiltered to remove Fe powder. The filtrate was alkalified with NaHCO₃,and washed many times with water. The organic layer was dried andfiltered, followed by purification by column chromatography(EA:hexane=1:1) packed with Et₃N-treated silica gel to afford the titlecompound as a yellow solid (144 mg, 68%).

¹H-NMR (300 MHz, CD₃OD) δ 1.19 (d, J=6.9 Hz, 6H), 2.85 (sept, J=6.6 Hz,1H), 6.67 (s, 1H), 6.69 (d, J=7.4 Hz, 1H), 6.90 (d, J=7.3 Hz, 1H), 7.02(d, J=7.4 Hz, 1H), 7.12 (s, 1H), 7.25 (s, 1H), 7.45-7.51 (m, 2H), 7.73(s, 1H).

<Example 292>N-(1-Amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)tetrazolo[1,5-a]pyridine-5-carboxamide

Fe powder (0.17 g, 3.08 mmol), conc. HCl (0.03 ml), and water (1 ml)were added in that order to a solution ofN-(4b-hydroxy-7-isopropyl-1-nitro-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)tetrazolo[1,5-a]pyridine-5-carboxamide(0.30 g, 0.61 mmol) in absolute ethanol (10 ml), and heated for 2 hrsunder reflux. The reaction mixture was washed with ethylacetate, and hotfiltered to remove Fe powder. The filtrate was alkalified with NaHCO₃,and washed many times with water. The organic layer was dried andfiltered, followed by purification for 30 min by column chromatography(ethylacetate:hexane=1:1) packed with Et₃N-treated silica gel to affordthe title compound. 0.11 g (40%).

¹H-NMR (300 MHz, CD₃OD) δ 1.18-1.23 (m, 6H, CH₃) 2.83-2.92 (sept, 1H,CH) 6.74 (m, 1H, ArH) 6.93 (d, J=7.5 Hz, 1H, ArH) 7.05 (d, J=6.9 Hz, 1H,ArH) 7.47-7.56 (m, 2H, ArH) 7.89 (s, 1H, ArH) 7.99 (t, J=7.2 Hz, 1H,ArH) 8.08 (d, J=7.2 Hz, 1H, ArH) 8.36 (d, J=7.8 Hz, 1H, ArH).

<Example 293>N-(1-Amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-1-methyl-1H-indazole-3-carboxamide

Fe powder (0.16 g, 2.92 mmol), conc. HCl (0.03 ml), and water (1 ml)were added in that order to a solution ofN-(4b-hydroxy-7-isopropyl-1-nitro-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-1-methyl-3a,7a-dihydro-1H-indazole-3-carboxamide(0.27 g, 0.54 mmol) in absolute ethanol (10 ml), and heated for 3 hrsunder reflux. The reaction mixture was washed with ethylacetate, and hotfiltered to remove Fe powder. The filtrate was alkalified with NaHCO₃,and washed many times with water. The organic layer was dried andfiltered, followed by purification for 30 min by column chromatography(ethylacetate:hexane=1:2) packed with Et₃N-treated silica gel to affordthe title compound. 0.13 g (52%).

¹H-NMR (300 MHz, CD₃OD) δ 1.19 (d, J=6.9 Hz, 6H, CH₃) 2.80-2.88 (sept,1H, CH) 4.12 (s, 1H, CH₃) 6.69-6.80 (m, 2H, ArH) 6.88 (d, J=6.9 Hz, 1H,ArH) 7.04 (d, J=6.6 Hz, 1H, ArH) 7.20-7.25 (m, 1H, ArH) 7.40-7.48 (m,3H, ArH) 7.59 (d, J=8.7 Hz, 1H, ArH) 8.07 (d, J=8.4 Hz, 1H, ArH).

<Example 294>N-(1-Amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-1H-indole-5-carboxamide

Fe powder (0.04 g, 0.82 mmol), conc. HCl (0.03 ml), and water (0.5 ml)were added in that order to a solution ofN-(4b-hydroxy-7-isopropyl-1-nitro-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-1H-indole-5-carboxamide(80 mg, 0.16 mmol) in absolute ethanol (5 ml) and heated for 3 hrs underreflux. The reaction mixture was washed with ethylacetate, and hotfiltered to remove Fe powder. The filtrate was alkalified with NaHCO₃,and washed many times with water. The organic layer was dried andfiltered, followed by purification for 30 min by column chromatography(ethylacetate:hexane=1:2) packed with Et₃N-treated silica gel to affordthe title compound. 35 mg (47%).

¹H-NMR (300 MHz, CD₃OD) δ 1.19 (d, J=7.2 Hz, 6H, CH₃) 2.80-2.88 (sept,1H, CH) 6.50-6.53 (m, 1H, ArH) 6.69-6.72 (m, 2H, ArH) 6.80-6.85 (m, 1H,ArH) 7.03-7.12 (m, 2H, ArH) 7.29-7.31 (m, 1H, ArH) 7.37-7.47 (m, 2H,ArH) 7.60-7.63 (m, 1H, ArH) 8.16 (s, 1H, ArH).

<Example 295>N-(1-Amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-1-methyl-3a,7a-dihydro-1H-indazole-3-carboxamide

Fe powder (0.08 g, 1.46 mmol), conc. HCl (0.03 ml), and water (1 ml)were added in that order to a solution ofN-(4b-hydroxy-7-isopropyl-1-nitro-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-3-methyl-[1,2,4]triazolo[4,3-a]pyridine-8-carboxamide(0.13 g, 0.20 mmol) in absolute ethanol (10 ml), and heated for 23 hrsunder reflux. The reaction mixture was washed with ethylacetate, and hotfiltered to remove Fe powder. The filtrate was alkalified with NaHCO₃,and washed many times with water. The organic layer was dried andfiltered, followed by purification for 30 min by column chromatography(ethylacetate 100%) packed with Et₃N-treated silica gel to afford thetitle compound. 44 mg (46%).

¹H-NMR (300 MHz, CD₃OD) δ 1.21 (d, J=6.9 Hz, 6H, CH₃) 2.77 (s, 3H, CH₃)2.84-3.30 (sept, 1H, CH) 6.71-6.79 (m, 2H, ArH) 6.90 (d, J=8.7 Hz, 1H,ArH) 7.03 (d, J=5.7 Hz, 1H, ArH) 7.13 (t, J=7.2 Hz, 1H, ArH) 7.46-7.48(m, 2H, ArH) 8.04 (d, J=6.3 Hz, 1H, ArH) 8.48 (d, J=7.2 Hz, 1H, ArH).

<Example 296>N-(1-Amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-1-methyl-1H-imidazole-4-carboxamide

Fe powder (0.09 g, 1.62 mmol), conc. HCl (0.03 ml), and water (1 ml)were added in that order to a solution ofN-(4b-hydroxy-7-isopropyl-1-nitro-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-1-methyl-1H-imidazole-4-carboxamide(0.10 g, 0.22 mmol) in absolute ethanol (10 ml), and heated for 3 hrsunder reflux. The reaction mixture was washed with ethylacetate, andfiltered to remove Fe powder. The filtrate was alkalified with NaHCO₃,and washed many times with water. The organic layer was dried andfiltered, followed by purification for 30 min by column chromatography(ethylacetate 100%) packed with Et₃N-treated silica gel to afford thetitle compound. 29 mg (31%).

¹H-NMR (300 MHz, CD₃OD) δ 1.18 (d, J=6.9 Hz, 6H, CH3) 2.80-2.86 (sept,1H, CH) 6.66-6.69 (m, 2H, ArH) 6.87 (d, J=7.2 Hz, 1H, ArH) 6.99 (d,J=7.2 Hz, 1H, ArH) 7.41-7.45 (m, 2H, ArH) 7.57-7.61 (m, 2H, ArH).

<Example 297>N-(1-Amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl-1H-pyrrole-3-carboxamide

Fe powder (31 mg, 0.55 mmoles) and 2 drops of conc. HCl weresequentially added to a solution ofN-(4b-hydroxy-7-isopropyl-4-nitro-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-1H-pyrrole-3-carboxamide(0.08 g, 0.18 mmoles) in an ethanol:water (10:1, 10 mL) solvent, andheated for 3 hrs under reflux. The reaction mixture was washed withethylacetate, and hot filtered to remove Fe powder. The filtrate wasconcentrated in a vacuum and purified by silica gel columnchromatography (30% ethylacetate mixed with 60% hexane) to afford thetitle compound. 35 mg (47%).

¹H-NMR (300 MHz, CD₃OD): δ 1.18 (d, J=6.9 Hz, 6H, CH₃) 2.84 (sept, 1H,CH) 6.53-6.58 (m, 1H, ArH) 6.64-6.76 (m, 3H, ArH) 6.86-6.90 (m, 1H, ArH)6.98-7.01 (m, 1H, ArH) 7.36-7.46 (m, 3H, ArH).

<Example 298>tert-Butyl(tert-butoxycarbonylamino)(4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-ylamino)methylenecarbamate

4b,9b-dihydroxy-7-isopropyl-4bH-benzo[d]indeno[1,2-b]furan-10(9bH)-one(0.30 g, 1.02 mmol) was dissolved in 5 ml of THF, and stirred, togetherwith DEAD (0.24 ml, 1.56 mmol and PPh₃(0.41 g, 1.56 mmol), for 5 min,and then together with, Boc-guanidine (0.40 g, 1.56 mmol for 3 hrs atroom temperature. Thereafter, vacuum concentration was performed,followed by purification by column chromatography(ethylacetate:hexane=1:2) to afford the title compound. 40 mg (7%).

¹H-NMR (300 MHz, CDCl₃) δ 1.15 (d, J=6.8 Hz, 6H), 1.30 (s, 9H), 1.50 (s,9H), 2.81 (q, J=7.3 Hz, 1H), 6.69 (s, 1H), 6.81 (d, J=7.5 Hz, 1H), 7.30(d, J=7.9 Hz, 1H), 7.51 (t, J=8.7 Hz, 1H), 7.67 (s, 1H), 7.73-7.82 (m,2H), 8.00 (d, J=7.9 Hz, 1H), 9.36 (s, 1H), 11.17 (s, 1H).

<Example 299>N-(1-Amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl-1H-indazole-5-carboxamide

Fe powder (104 mg, 1.86 mmol and 4 drops of conc. HCl were sequentiallyadded to a solution ofN-(4b-hydroxy-7-isopropyl-1-nitro-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl-1H-indazole-5-carboxamide(300 mg, 0.62 mmol in an ethanol:H₂O (20 ml:2 ml) solvent, and heatedfor 3 hrs under reflux. After vacuum concentration, purification bycolumn chromatography (EtOAc:Hexane=2:1) afforded the title compound asa yellow solid. 90 mg (32%).

¹H-NMR (300 MHz, CD₃OD) δ 1.19 (d, J=6.8 Hz, 6H, CH₃), 2.85 (m, 1H, CH),6.67-6.74 (m, 2H, ArH), 6.89 (d, J=8.0 Hz, 1H, ArH), 7.02 (d, J=7.4 Hz,1H, ArH), 7.43-7.56 (m, 3H, ArH), 7.85-7.88 (m, 1H, ArH), 8.13 (s, 1H,ArH), 8.38 (s, 1H, ArH).

<Example 300>N-(1-Amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-3-methyl-1H-pyrazole-5-carboxamide

Fe powder (36 mg, 0.65 mmol) and 2 drops of conc. HCl were sequentiallyadded to a solution ofN-(4b-hydroxy-7-isopropyl-1-nitro-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)-3-methyl-1H-pyrazole-5-carboxamide(90 mg, 0.22 mmol) in an ethanol:H₂O (10 ml:1 ml) solvent, and heatedfor 3 hrs under reflux. After vacuum concentration, purification bycolumn chromatography (EtOAc:Hexane=1:2) afforded the title compound asa yellow solid. 62 mg (74%).

¹H-NMR (300 MHz, CD₃OD) δ 1.18 (d, J=6.9 Hz, 1H, CH₃), 2.29 (s, 3H,CH₃), 2.84 (sep, J=6.9 Hz, 1H, CH), 6.42 (s, 1H, ArH), 6.66-6.70 (m, 2H,ArH), 6.87 (d, J=8.0 Hz, 1H, ArH), 6.99 (d, J=7.4 Hz, 1H, ArH),7.41-7.47 (m, 2H, ArH).

<Example 301>1-Amino-9b-(furane-2-carboxamido)-7-methoxy-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-4b-ylfurane-2-carboxylate

HATU (0.35 g, 3.52 mmol) was added at 0° C. to a solution offurane-2-carboxylic acid (0.20 g, 1.85 mmol) in anhydrousdimethylformamide (3 ml) which was then stirred, together with Et₃N(0.70 g, 1.85 mmol) and9b-amino-4b-hydroxy-7-methoxy-4bH-indeno[1,2-b]benzofuran-10(9bH)-one(0.50 g, 1.76 mmol), at room temperature for 24 hrs. The reactionmixture was diluted in ethylacetate and washed many times with anaqueous K₂CO₃ solution and brine, and the organic layer was dried andfiltered. Purification by column chromatography(ethylacetate:hexane=1:1) afforded the title compound. 13 mg (1.5%).

¹H-NMR (300 MHz, CDCl₃) δ 3.76 (m, 3H, OMe), 6.39-6.50 (m, 2H, ArH),6.65 (m, 1H, ArH), 6.93-6.95 (m, 2H, ArH), 7.12 (d, J=3.9 Hz, 1H, ArH)7.38 (s, 1H, ArH), 7.47 (s, 1H, ArH), 7.51-7.54 (m, 1H, ArH), 7.63 (t,J=7.5 Hz, 1H, ArH) 7.84 (t, J=7.2 Hz, 1H, ArH) 7.93 (d, J=7.5 Hz, 1H,ArH), 8.09 (t, J=7.8 Hz, 1H, ArH).

<Example 302>N-(4b-hydroxy-7,8-dimethyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-ylnicotinamide

A solution of nicotinic acid (409 mg, 2.14 mmol in DCM was cooled to 0°C. It was stirred, together with EDCl (332 mg, 2.14 mmol, for 10 min,then together with DMF (3 mL) for an additional 10 min, and finallytogether with HOBt (289 mg, 2.14 mmol and9b-amino-4b-hydroxy-7,8-dimethyl-4bH-indeno[1,2-b]benzofuran-10(9bH)-one(500 mg, 1.78 mmol for 15 hrs at room temperature. Subsequently, thereaction mixture was mixed with DCM, washed with water, and dehydratedwith Na₂SO₄. After filtration and concentration, purification by columnchromatography afforded the title compound as a solid. 178 mg (26%).

¹H-NMR (300 MHz, CD₃OD) δ 2.19 (s, 3H), 2.22 (s, 3H), 6.60 (s, 1H), 7.29(s, 1H), 7.49-7.52 (m, 1H), 7.66-7.88 (m, 4H), 8.25 (d, J=2.1 Hz, 1H),8.66 (d, J=3.4 Hz, 1H), 8.99 (s, 1H).

<Example 303>N-(4b-hydroxy-7,8-dimethyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl-1H-pyrrole-2-carboxamide

9b-Amino-4b-hydroxy-7,8-dimethyl-4bH-indeno[1,2-b]benzofuran-10(9bH)-one(500 mg, 1.78 mmol and 1H-pyrrole-2-carboxylic acid (238 mg, 2.14 mmolwere dissolved in DCM (17.8 mL, 0.1 M), mixed with DCC (442 mg, 2.14mmol at room temperature while stirring. The reaction mixture was washedwith water, dehydrated with Na₂SO₄, filtered, and concentrated, followedby purification by column chromatography to afford the title compound asa solid. 40 mg (6%).

¹H-NMR (300 MHz, CD₃OD) δ 2.17 (s, 3H), 2.19 (s, 3H), 6.3-6.15 (m, 1H),6.58 (s, 1H), 6.88 (s, 1H), 6.92 (d, J=3.7 Hz, 1H), 7.28 (s, 1H),7.54-7.59 (m, 1H), 7.75-7.82 (m, 1H), 7.91-7.93 (m, 1H).

<Example 304>N-(6-ethyl-4b-hydroxy-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl-1H-pyrrole-2-carboxamide

Pyrrole-2-carboxylic acid (133 mg, 1.96 mmol) and9b-amino-6-ethyl-4b-hydroxy-4bH-benzo[d]indeno[1,2-b]furan-10(9bH)-one(500 g, 1.78 mmol were together dissolved in methylene chloride (10 ml),and mixed with DCC (367 mg, 1.78 mmol) at room temperature for 20 hrswhile stirring. After extraction with CH₂Cl₂ and water, the organiclayer was dried over MgSO₄ and concentrated in a vacuum. Purification bycolumn chromatography (EA:Hex=1:1) afforded the title compound as ayellow solid. 151 mg (23%).

¹H-NMR (300 MHz, CDCl₃) δ 1.17 (t, J=7.5 Hz, 3H, CH₃), 2.64 (q, J=7.5Hz, 2H, CH₂), 5.93 (s, 1H, OH), 6.26 (s, 1H, ArH), 6.79 (s, 1H, ArH),6.85-6.98 (m, 3H, ArH), 7.21-7.26 (m, 1H, ArH), 7.56 (t, J=7.6 Hz, 1H,ArH), 7.80-7.85 (m, 2H, ArH), 8.04 (d, J=7.8 Hz, 1H, ArH).

<Example 305>N-(6-ethyl-4b-hydroxy-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)furane-2-carboxamide

Furane-2-carboxylic acid (239 mg, 2.13 mmol) was dissolved in methylenechloride (10 ml), and mixed with EDCl (406 mg, 2.13 mmol) and HOBt (288mg, 2.13 mmol) for 10 min, and then with9b-amino-6-ethyl-4b-hydroxy-4bH-benzo[d]indeno[1,2-b]furan-10(9bH)-one(500 mg, 1.78 mmol) overnight at room temperature while stirring. Afterextraction with CH₂Cl₂ and water, the organic layer was dried over MgSO₄and concentrated in a vacuum. Purification by column chromatography(EA:Hex=1:2) afforded the title compound as a yellow solid. 180 mg(27%).

¹H-NMR (300 MHz, CDCl₃) δ 1.17 (t, J=7.5 Hz, 3H, CH₃), 2.63 (q, J=7.5Hz, 2H, CH₂), 5.63 (br, 1H, OH), 6.51 (q, 1.7 Hz, 1H, ArH), 6.89 (t,J=7.6 Hz, 1H, ArH), 7.09-7.14 (m, 2H, ArH), 7.23-7.26 (m, 1H, ArH), 7.46(s, 1H, NH), 7.52 (s, 1H, ArH), 7.56 (t, J=7.5 Hz, 1H, ArH), 7.79-7.85(m, 2H, ArH), 8.04 (d, J=7.8 Hz, 1H, ArH).

<Example 306>N-(8-chloro-4b-hydroxy-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)quinoline-4-carboxamide

Quinoline-4-carboxylic acid (361 mg, 1.74 mmol) was dissolved inmethylene chloride (10 ml), and mixed with EDCl (397 mg, 2.08 mmol) andHOBt (281 mg, 2.08 mmol) for 10 min and then with9b-amino-6-ethyl-4b-hydroxy-4bH-benzo[d]indeno[1,2-b]furan-10(9bH)-one(500 mg, 1.74 mmol) overnight at room temperature while stirring. Afterextraction with CH₂Cl₂ and water, the organic layer was dried over MgSO₄and concentrated in a vacuum. Purification by column chromatography(EA:Hex=1:1) afforded the title compound as a white solid. 112 mg (15%).

¹H-NMR (500 MHz, CDCl₃) δ 6.86 (d, J=8.6 Hz, 1H ArH), 7.19 (s, 1H, NH),7.27˜7.29 (m, 1H, ArH), 7.43 (d, J=2.1 Hz, 1H, ArH), 7.53 (d, J=4.2 Hz,1H, ArH), 7.60-7.65 (m, 2H, ArH), 7.78 (t, J=7.9 Hz, 1H, ArH), 7.87-7.91(m, 2H, ArH), 8.06-8.11 (m, 2H, ArH), 8.16 (d, J=8.1 Hz, 1H, ArH), 8.98(d, J=4.2 Hz, 1H, ArH).

<Example 307>N-(8-Chloro-4b-hydroxy-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)tetrahydrofurane-2-carboxamide

Tetrahydrofurane-2-carboxylic acid (242 mg, 2.08 mmol) was dissolved inmethylene chloride (10 ml), and mixed with EDCl (397 mg, 2.08 mmol) andHOBt (281 mg, 2.08 mmol) for 10 min and then with9b-amino-6-ethyl-4b-hydroxy-4bH-benzo[d]indeno[1,2-b]furan-10(9bH)-one(500 mg, 1.74 mmol) overnight at room temperature while stirring. Afterextraction with CH₂Cl₂ and water, the organic layer was dried over MgSO₄and concentrated in a vacuum. Purification by column chromatography(EA:Hex=1:1) afforded the title compound as a yellow solid. 183 mg(27%).

¹H-NMR (300 MHz, CDCl₃) δ 1.88-1.95 (m, 3H, CH₂), 2.17-2.30 (m, 1H,CH₂), 3.88-3.95 (m, 1H, OCH₂), 3.98-4.09 (m, 1H, OCH₂), 4.29-4.40 (m,1H, OCH), 6.75-6.77 (m, 1H, ArH), 7.19-7.21 (m, 1H, ARH), 7.30-7.34 (m,1H, ArH), 7.57 (t, J=7.3 Hz, 1H, ArH), 7.79-7.84 (m, 2H, ArH), 7.97-7.99(m, 1H, ArH).

In Table 1, chemical formulas of compounds of Examples 1 to 307 areshown.

TABLE 1 Ex. Chemical Structure 1

2

3

4

5

6

7

8

9

10

11

12

13

14

15

16

17

18

19

20

21

22

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<Experimental Example 1> Cytopathic Effect (CPE) Inhibition Assay forAntiviral Activity Against Picornaviruses

In the assay, HeLa (human cervical cancer cells), MRC-5 (human fetallung fibroblast cells), and RD cells (derived from humanrhabdomyosarcoma) were employed. For comparison, ribavirin (Riv),pleconaril (pleco), and BTA-798 (BTA) were used as controls. Reagentswere dissolved at a concentration of 10˜40 mg/ml in 100%dimethylsulfoxide (DMSO). Water-soluble reagents were dissolved in PBS(−) solution and stored at −20° C. On the day of the experiment, theywere used in 3× to 5× concentrations in such a manner that theconcentration of dimethylsulfoxide in each well was between 0.5% and 1%.

Pharmaceutical effects were determined using a virus-induced cytopathiceffect (CPE) inhibition assay. In this regard, after cells suitable forviruses were grown in 96-well plates, dilutions of viruses in DMEsupplemented with 2% FBS (DME/2% FBS) or MEM supplemented with 2% FBS(MEM/2% FBS) were inoculated in an amount of 100 μl with a concentrationcorresponding to 100 CCID₅₀ (50% cell culture infective dose) into eachwell of the plates, and incubated for 30 min˜1 hrs at 33° C. or 37° C.to allow the viruses to adosorb to the cells. The culture medium wasremoved before aliquots of drug dilutions with various concentrationswere added in an amount of 100 μl to each well. While HRV was grown at33° C., the other viruses were incubated in a 37° C. CO₂ incubator for2˜3 days. Alternatively, the cells were cultured for 2˜3 days withoutremoval of the medium after they were added with 50 μl of each drugdilution having a 2-fold higher concentration and then with 50 μl of thevirus dilution.

Test conditions for each virus are summarized in Table 2, below.

TABLE 2 Incu- Host bation Incubation Virus Note cell Temp. Term MediumCoxsackie A9 — RD 37° C. 2 days MEM/2% FBS Coxsackie — MRC-5 37° C. 2days MEM/2% FBS A24 Coxsackie Isolated MRC-5 37° C. 2 days MEM/2% FBSA24 from patients Coxsackie B1 — HeLa 37° C. 2 days DME/2% FBS CoxsackieB3 — HeLa 37° C. 2 days DME/2% FBS Coxsackie B4 — HeLa 37° C. 2 daysDME/2% FBS Entero 70 — MRC-5 37° C. 2 days MEM/2% FBS Poliovirus3 — HeLa37° C. 2 days DME/2% FBS Rhinovirus — HeLa 33° C. 3 days MEM/2% FBS

For HeLa cells, the drugs were measured for EC₅₀ (50% maximal effectiveconcentration), which is the concentration of a drug inducing a responsehalfway between the baseline and maximum, using an MTT assay. Withregard to RD and MRC-5 cells, CPE was determined using FDA (Fluoresceindiacetate). In order for the evaluation results of drug potency toreflect the toxic effect of the drug, mock-infected cells which wereprepared by adding a virus-free medium to a cell culture were treated inthe same manner. That is, the medium was removed after one hour ofincubation, and dilutions of drugs in the medium were added once more.Following incubation for 2˜3 days, the cells were observed under amicroscope and the drugs were determined for CC₅₀ (50% cytotoxicconcentration), using an MTT assay in which counts of viable cells inmock-infected wells containing drugs were compared to those of viablecells in control wells containing no drugs. In an FDA hydrolysis assay,FDA was added to each well after removal of the medium, and incubatedfor 20˜30 min before fluorescence intensity was measured using aspectrofluorimeter to determine CPE in the same manner as in MTT.

Survival rate (% survival) of mock-infected cells was calculated usingthe following Mathematic Formula 1:

$\begin{matrix}{{{Cell}\mspace{14mu}{Survival}\mspace{14mu}{by}\mspace{14mu}{Drug}} = {\frac{{A({Drug})} - {A\left( {{Background}\mspace{14mu}{Sol}^{\prime}n} \right)}}{{A\left( {{Cell}\mspace{14mu}{Control}} \right)} - {A\left( {{Bakground}\mspace{14mu}{Sol}^{\prime}n} \right)}} \times 100\%}} & \left\lbrack {{Mathmatic}\mspace{14mu}{Formula}\mspace{14mu} 1} \right\rbrack\end{matrix}$

While 100% cell survival means no cytotoxicity of the drug, the highestcytotoxicity is reflected by 0% cell survival. The 50% cytotoxicconcentration (CC₅₀) was defined as the concentration required to reducethe cell number by 50% compared to that for the untreated controls.Higher CC₅₀ values mean lower cytotoxicity.

In addition, antiviral effects can be calculated using the followingMathematic Formula 2:

$\begin{matrix}{{{Antiviral}\mspace{14mu}{Effect}} = {\frac{{A\left( {{Drug}/{Virus}} \right)} - {A\left( {{Virus}\mspace{14mu}{Control}} \right)}}{{A\left( {{Cell}\mspace{14mu}{Control}} \right)} - {A\left( {{Virus}\mspace{14mu}{Control}} \right)}} \times 100\%}} & \left\lbrack {{Mathmatic}\mspace{14mu}{Formula}\mspace{14mu} 2} \right\rbrack\end{matrix}$

A survival rate of 100% means a perfect antiviral effect (100%) whereasthe drugs are regarded to be devoid of antiviral effects at a survivalrate of 0%. The viral cytopathic effect (CPE) was recorded, and the 50%effective concentration (EC₅₀) was defined as the compound concentrationrequired to reduce the viral CPE by 50% compared to that for theuntreated control. Lower EC₅₀ values mean higher antiviral activities.

CC₅₀ and EC₅₀ values of the compounds which account cytotoxicity andantiviral activity against picornaviruses, respectively, are given inTables 3 and 4.

TABLE 3 Coxsackie Coxsackie Coxsackie Coxsackie Coxsackie A24(DN)A24(HG) Poliovirus Poliovirus Ex. CC₅₀ B1 EC₅₀ B3 EC₅₀ B4 EC₅₀ EC₅₀ EC₅₀3 EC₅₀ 2 EC₅₀ No. (μg/mL) (μg/mL) (μg/mL) (μg/mL) (μg/mL) (μg/mL)(μg/mL) (μg/mL) 43 33.17 <0.01 — <0.01 — — — — 47 15.38 <0.01 <0.01 —0.055 <0.01 <0.1 — 50 49.89 <0.01 <0.01 — — — <0.1 — 71 38.85 <0.01<0.01 <0.01 0.1 0.056 <0.1 <0.1 74 9.26 <0.01 <0.01 — 0.36 0.34 — —

TABLE 4 Rhino Rhino Rhino Picorana Coxsackie Coxsackie Poliovirus3 RhinoHRV14 HRV21 HRV71 Ex. CC₅₀ B1 EC₅₀ B3 EC₅₀ EC₅₀ CC₅₀ EC₅₀ EC₅₀ EC₅₀ No.(μg/mL) (μg/mL) (μg/mL) (μg/mL) (μg/mL) (μg/mL) (μg/mL) (μg/mL) 1 >500.026 — — — — — — 2 >50 — 0.02 — — — — — 3 >50 — — — — — — — 4 >50 —0.019 — — — — — 5 >50 — — — — — — — 6 47.51 — — — — — — — 7 >50 — — — —— — — 8 44.1 — — — — — — — 9 18 <0.01 0.027 — — — — — 10 14.2 <0.01<0.01 — 18.43 — — <1.0 11 16.2 <0.01 <0.01 — — — — — 12 >50 — — — — — —— 13 8.08 — — — — — — — 14 >50 — — — — — — — 15 8.57 — — — — — — — 167.82 — — — — — — — 17 7.85 — — — — — — — 18 37.48 — — — — — — — 19 8.34— — — — — — — 20 7.93 — — — — — — — 21 32.1 — — — — — — — 22 8.01 — — —— — — — 23 9.3 — — — — — — — 24 8.8 0.013 — — — — — — 25 >50 — — — — — —— 26 <4 — — — — — — — 27 43.9 — — — — — — — 28 9.2 — — — — — — — 29 7.490.355 — — — — — — 30 45.5 0.014 — — — — — — 31 8.9 — — — — — — — 32 8.1— — — — — — — 33 >50 — — — — — — — 34 >50 — — — — — — — 35 46.69 <0.01 —— — — — — 36 9.34 <0.01 — — — — — — 37 9.68 <0.01 — — — — — — 38 9.5<0.01 — — — — — — 39 45.12 — — — — — — — 40 43.96 <0.01 — — — — — — 4127.14 <0.01 — — — — — — 42 8.94 — — — — — — — 43 33.17 <0.01 — — — — — —44 6.25 — — — — — — — 45 12.23 <0.01 — — — — — — 46 9.42 <0.01 — <0.0118.33 <0.01 — — 47 15.38 <0.01 <0.01 <0.1 — — — — 48 35.01 — — — — — — —49 9.18 0.373 — — — — — — 50 49.89 <0.01 <0.01 <0.1 — — — — 51 17.47<0.01 <0.01 — — — — — 52 >50 — — — — — — — 53 45.65 0.04 — — — — — —54 >50 0.014 0.0147 — — — — — 55 7.49 0.084 — — — — — — 56 42.16 0.0784— — — — — — 57 46.66 0.35 — — — — — — 58 >50 — — — — — — — 59 >50 — — —— — — — 60 10.56 <0.01 <0.01 — — — — — 61 >50 <0.01 <0.01 — — — — —62 >50 <0.01 <0.01 — — — — — 63 >50 <0.01 — — — — — — 64 8.13 <0.01<0.01 — — — — — 65 18.19 <0.01 0.015 — — — — — 66 44.72 <0.01 <0.01 — —— — — 67 9.42 0.596 — — — — — — 68 8.94 <0.01 <0.01 — — — — — 69 70 0.43— — — — — — 70 47.08 <0.01 <0.01 — — — — — 71 38.85 <0.01 <0.01 <0.1 — —— — 72 43.91 <0.01 <0.01 — — — — — 73 47.08 <0.01 <0.01 <0.01 56.4 <0.01<1.0 <1.0 74 9.26 <0.01 <0.01 — — — — — 75 46.66 <0.01 <0.01 — — — — —76 >50 — — — — — — — 77 >50 <0.01 <0.01 — 53.86 <0.01 — — 78 47.74 0.025— — 20.65 <0.01 — — 79 10.43 — — — — — — — 80 47.51 0.0139 — — — — — —81 8.61 — — — — — — — 82 1.9 — — — — — — — 83 46.25 — — — — — — — 84 >50— — — — — — — 85 19.25 — — — — — — — 86   — — — — — — — 87 36.77 <0.01<0.01 — — — — — 88 8.16 0.017 — — — — — — 89 >50 <0.01 <0.01 — — — — —90 33.95 <0.01 <0.01 — — — — — 91 >50 — — — — — — — 92 >50 — — — — — — —93 8.49 <0.01 <0.01 — 6.23 <0.01 — — 94 42.39 <0.01 <0.01 — 58.06 <0.01— — 95 38.07 <0.01 <0.01 — 25.99 <0.01 — — 96 >50 <0.01 <0.01 0.01623.97 <0.01 — — 97 >50 <0.01 <0.01 — 8.8 <0.01 — — 98 7.8 <0.01 0.022 —— — — — 99 >50 <0.01 <0.01 — 7.7 0.0101 — — 100 40.64 — — — — — — —101 >50 — — — — — — — 102 >50 — — — — — — — 103 >50 — — — — — — —104 >50 0.015 — — — — — — 105 >50 0.018 0.016 — — — — — 106 3.53 — — — —— — — 107 >50 — — — — — — — 108 1.81 — — — — — — — 109 >50 — — — — — — —110 14.41 — — — — — — — 111 43.58 <0.01 <0.01 — — — — — 112 41.98 <0.01<0.01 — — — — — 113 45.46 <0.01 <0.01 <0.01 48.78 <0.01 <1.0 — 114 45.85<0.01 <0.01 0.034 43.12 <0.01 — — 115 42.79 <0.01 <0.01 <0.01 23.11<0.01 — — 116 41.72 <0.01 <0.01 — — — — — 117 >50 0.012 — — — — — —118 >50 <0.01 <0.01 — — — — — 119 38.22 0.027 — — — — — — 120 8.16 — — —— — — — 121 >50 0.02 — — — — — — 122 11.96 — — — — — — — 123 37.54 <0.01<0.01 <0.01 43.35 <0.01 <1.0 — 124 >50 — — — — — — — 125 45.46 — — — — —— — 126 47.06 — — — — — — — 127 37.61 — — — — — — — 128 37.31 — — — — —— — 129 6.79 — — — — — — — 130 >50 — — — — — — — 131 2.05 <0.01 <0.01 —— — — — 132 0.72 0.03 — — — — — — 133 1.58 <0.01 — — — — — — 134 6.69 —— — — — — — 135 10.94 — — — — — — — 136 7.8 — — — — — — — 137 39.97<0.01 <0.01 — — — — — 138 38.8 — — — — — — — 139 0.45 — — — — — — — 1402.08 — — — — — — — 141 3.47 — — — — — — — 142 18.68 — — — — — — —143 >50 <0.01 <0.01 <0.01 58.06 <0.01 <1.0 — 144 35.48 <0.01 <0.01 <0.0121.71 <0.01 <1.0 — 145 18.33 0.026 — — — — — — 146 1.53 — — — — — — —147 32.88 — — — — — — — 148 1.72 — — — — — — — 149 8.48 — — — — — — —150 1.32 — — — — — — — 151 1.52 0.04 — — — — — — 152 0.9 — — — 10.52 — —— 153 9.02 <0.01 <0.01 <0.01 16.03 <0.01 <1.0 <1.0 154 46.23 <0.01 <0.01<0.01 22.71 <0.01 <1.0 <1.0 155 9.02 <0.01 <0.01 <0.01 7.81 <0.01 <1.0<1.0 156 36.38 <0.01 <0.01 <0.01 >10 <0.01 <1.0 <1.0 157 >100 <0.01<0.01 — 28.49 — — — 158 44.72 <0.01 <0.01 <0.01 39.42 <0.01 <1.0 — 15944.72 0.021 — — 42.39 — — — 160 47.19 <0.01 <0.01 — 18.52 — — — 16140.73 <0.01 <0.01 <0.01 17.89 <0.01 <1.0 — 162 >10 — — — >10 — — —163 >10 — — — >10 — — — 164 >10 0.04 0.04 — >10 — — — 165 >10 <0.01<0.01 — >10 <0.01 — — 166 >10 <0.01 <0.01 <0.01 >10 <0.01 <1.0 <1.0167 >10 <0.01 0.034 — >10 0.038 — — 168 >10 0.04 — — >10 — — — 169 >10 —— — >10 — — — 170 >10 <0.01 <0.01 <0.01 >10 <0.01 <1.0 <1.0 171 >10<0.01 <0.01 0.03 >10 — <1.0 <1.0 172 >10 <0.01 0.027 — >10 0.0125 — —173 >10 0.036 — — >10 — — — 174 >10 <0.01 <0.01 0.019 >10 <0.01 — —175 >11 <0.01 <0.01 <0.01 >10 <0.01 — — 176 >10 0.037 0.037 — >10 — — —177 >10 <0.01 <0.01 — >10 <0.01 — — 178 >10 <0.01 0.035 — >10 — — —179 >10 <0.01 <0.01 <0.01 >10 <0.01 <1.0 — 180 4.32 <0.01 <0.010.033 >10 0.0114 — — 181 >10 <0.01 <0.01 0.036 >10 0.0124 — — 182 6.42<0.01 0.022 — 5.85 0.035 — — 183 8.54 <0.01 <0.01 0.014 >10 <0.01 — —184 36.38 <0.01 0.025 — >10 — — — 185 7.18 0.028 — — >10 — — — 186 8.31<0.01 <0.01 0.026 >10 <0.01 — — 187 7.43 <0.01 <0.01 <0.01 >10 <0.01<1.0 <1.0 188 8.38 <0.01 <0.01 <0.01 >10 <0.01 <1.0 <1.0 189 8.56 <0.01<0.01 <0.01 >10 <0.01 <1.0 <1.0 190 >10 <0.01 <0.01 <0.01 5.52 <0.01<1.0 <1.0 191 4.12 <0.01 <0.01 <0.01 >10 <0.01 — <1.0 192 >10 <0.01<0.01 — >10 — — — 193 >10 <0.01 <0.01 0.011 >10 <0.01 <1.0 — 194 >10<0.01 <0.01 — >10 <0.01 — — 195 — — — — — — — — 196 48.47 <0.01 <0.01 —16.18 — — — 197 34.45 <0.01 <0.01 <0.01 16.03 <0.01 — — 198 >50 <0.01<0.01 <0.01 27.94 <0.01 <1.0 <1.0 199 48.28 <0.01 <0.01 <0.01 42.95<0.01 <1.0 <1.0 200 >10 <0.01 <0.01 <0.01 >10 <0.01 <1.0 <1.0 201 >10<0.01 <0.01 <0.01 >10 <0.01 <1.0 <1.0 202 9.6 <0.01 <0.01 — 3.24 <0.01 —— 203 >10 <0.01 <0.01 <0.01 >10 <0.01 <1.0 <1.0 204 >4.51 <0.01 <0.010.011 >10 <0.01 — <1.0 205 >10 <0.01 <0.01 0.036 >10 <0.01 — — 206 >10<0.01 <0.01 <0.01 >10 <0.01 <1.0 <1.0 207 >10 <0.01 <0.01 <0.01 >10<0.01 <1.0 — 208 >10 <0.01 <0.01 — >10 <0.01 — — 209 >10 <0.01 <0.010.036 8.43 <0.01 — — 210 >10 <0.01 <0.01 — >10 — — — 211 >10 <0.01 <0.01— >10 0.039 — — 212 >10 <0.01 <0.01 <0.01 >10 <0.01 — <1.0 213 >10 <0.01<0.01 <0.01 >10 <0.01 <1.0 <1.0 214 >10 <0.01 <0.01 <0.01 >10 <0.01 <1.0<1.0 215 >10 <0.01 <0.01 <0.01 >10 <0.01 <1.0 — 216 4.75 0.036 0.037 —9.69 — — — 217 4.24 <0.01 <0.01 0.038 >10 <0.01 — — 218 8.49 <0.01 <0.01— >10 <0.01 — — 219 45.12 <0.01 <0.01 — >10 <0.01 — — 220 >50 — — — >10— — — 221 14.5 <0.01 <0.01 0.016 6.53 <0.01 — — 222 39.43 <0.01 <0.01— >10 0.037 — — 223 7.46 <0.01 <0.01 <0.01 4.36 — — — 224 >50 <0.010.013 — >10 — — — 225 22.87 <0.01 <0.01 — >10 — — — 226 28.18 <0.01<0.01 — >10 — — — 227 9.62 <0.01 <0.01 — >10 — — — 228 24.08 <0.01 <0.01— >10 0.029 — — 229 8.63 <0.01 <0.01 — 4.51 0.036 — — 230 42.83 <0.01<0.01 — >10 <0.01 <1.0 — 231 8.64 <0.01 <0.01 <0.01 >10 <0.01 — —232 >50 0.012 0.024 — >10 — — — 233 31.89 <0.01 <0.01 <0.01 >10 <0.01<1.0 <1.0 234 9.1 <0.01 <0.01 <0.01 >10 <0.01 <1.0 <1.0 235 7.97 <0.01<0.01 <0.01 8.88 <0.01 <1.0 <1.0 236 21.36 — — — >10 — — — 237 6.27 — —— >10 — — — 238 8.33 <0.01 <0.01 <0.01 >10 <0.01 <1.0 — 239 >50 <0.01<0.01 — >10 — — — 240 8.25 <0.01 <0.01 <0.01 >10 <0.01 — — 241 7.86<0.01 <0.01 — >10 — — — 242 8.55 <0.01 <0.01 <0.01 >10 <0.01 <1.0 <1.0243 7.36 <0.01 <0.01 <0.01 >10 <0.01 — — 244 15.71 <0.01 <0.01 <0.01 >10<0.01 — <1.0 245 8.47 <0.01 <0.01 <0.01 >10 <0.01 <1.0 <1.0 246 9.84<0.01 <0.01 <0.01 >10 <0.01 — — 247 20 <0.01 0.013 — >10 0.036 — — 2484.99 <0.01 <0.01 0.027 >10 <0.01 — — 249 >10 <0.01 <0.01 <0.01 >10 <0.01<1.0 <1.0 250 >10 <0.01 <0.01 <0.01 >10 <0.01 <1.0 <1.0 251 >10 <0.01<0.01 <0.01 >10 <0.01 <1.0 — 252 3.64 <0.01 <0.01 <0.01 3.53 <0.01 — —253 >10 <0.01 <0.01 <0.01 >10 <0.01 — — 254 >10 <0.01 <0.01 — >10 <0.01— — 255 >10 <0.01 <0.01 <0.01 >10 <0.01 <1.0 <1.0 256 >10 <0.01 <0.01<0.01 >10 <0.01 <1.0 <1.0 257 >10 <0.01 <0.01 0.031 >10 <0.01 — —258 >10 <0.01 <0.01 0.04 >10 <0.01 <1.0 — 259 >10 <0.01 <0.01 <0.01 >10<0.01 <1.0 <1.0 260 >10 <0.01 <0.01 0.04 >10 <0.01 — — 261 >10 <0.01<0.01 <0.01 >10 <0.01 <1.0 <1.0 262 >10 <0.01 <0.01 0.0124 >10 <0.01 — —263 7.65 <0.01 <0.01 0.039 5.4 <0.01 — — 264 >10 0.011 0.035 — >10 0.034— — 265 4.75 <0.01 <0.01 <0.01 4.4 <0.01 <1.0 <1.0 266 6.41 <0.01 <0.01<0.01 >10 <0.01 — — 267 0.87 <0.01 <0.01 — 0.86 0.012 <1.0 <1.1 268 9.28<0.01 <0.01 0.036 >10 <0.01 — <1.0 269 >10 0.018 0.035 — >10 0.036 — —270 6.57 0.03 0.036 — 5.93 0.039 — — 271 >10 <0.01 <0.01 <0.01 >10 <0.01<1.0 <1.0 272 >10 <0.01 <0.01 <0.01 >10 <0.01 <1.0 <1.0 273 >10 <0.01<0.01 <0.01 >10 <0.01 <1.0 <1.0 274 >10 <0.01 0.027 0.036 >10 <0.01 —<1.0 275 4.78 <0.01 <0.01 0.035 4.55 <0.01 — — 276 >10 <0.01 <0.01<0.01 >10 <0.01 <1.0 <1.0 277 >10 <0.01 <0.01 — >10 0.026 — — 278 >10<0.01 <0.01 <0.01 >10 <0.01 <1.0 <1.0 279 7.88 <0.01 <0.01 0.035 4.94<0.01 <1.0 <1.0 280 >10 <0.01 <0.01 — >10 <0.01 — — 281 >10 <0.01 <0.010.025 >10 <0.01 — — 282 6.78 <0.01 0.011 — >10 0.011 — — 283 5.47 0.024— — >10 0.024 — — 284 4.56 <0.01 0.016 — 3.71 0.028 — — 285 >10 <0.01<0.01 <0.01 >10 <0.01 <1.0 — 286 4.28 <0.01 <0.01 <0.01 4.04 <0.01 <1.0<1.0 287 7.01 <0.01 <0.01 0.036 >10 <0.01 — — 288 >10 <0.01 <0.010.029 >10 <0.01 — <1.0 289 >10 <0.01 <0.01 — >10 <0.01 <1.0 <1.0 2904.32 <0.01 <0.01 0.032 4.51 <0.01 <1.0 <1.0 291 4.43 <0.01 <0.01 0.0364.51 <0.01 <1.0 <1.0 298 >100 — — — — — — —

As is understood from data of Tables 3 and 4, most of the indanonederivatives of the present invention exhibited low cytotoxicity becausethey had high CC₅₀ values. In addition, most of the indanone derivativesof the present invention were found to be highly inhibitory ofcoxsackie-, polio- and rhinoviruses because their EC₅₀ values were 0.01μg/mL or less.

Accordingly, the indanone derivatives represented by Chemical Formula 1in accordance with the present invention exhibit low cytotoxicity andhigh inhibitory activity against a broad spectrum of picornaviruses, andthus may be usefully applied to a pharmaceutical composition forpreventing or treating picornavirus-caused diseases.

<Experimental Example 2> Multicycle Cytopathic Effect (CPE) ReductionAssay for Antiviral Effect Against Picornaviruses

The test compounds were evaluated for anti-picornavirus activity by amulticycle cytopathic effect (CPE) reduction assay. The antiviralactivity was initially determined using an MTS[3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl-2H-tetrazolium]-basedCPE reduction assay.

In this regard, cells grown to confluence in 96-well plates wereinfected with 100 50% cell culture infective doses (CCID₅₀) of virus.After an adsorption period of 2 hrs at 37° C., virus was removed andserial dilutions of the compounds were added. The cultures were furtherincubated at 37° C. for 3 days, until complete CPE was observed in theinfected and untreated virus control (VC). After removal of the medium,90 μl of a culture medium and 10 μl of MTS-phenazine methosulfate(Promega, Leiden, The Netherlands) were added to each well. After anincubation period of 2 hrs at 37° C., the optical density (OD) of eachwell was read at 498 nm in a microplate reader.

CPE values for evaluating antiviral activity were calculated using thefollowing Mathematic Formula 3:

$\begin{matrix}{{\%\mspace{14mu}{CPE}} = {100 \times \frac{{OD}_{CC} - {OD}_{{virus} + {compound}}}{{OD}_{CC} - {OD}_{VC}}}} & \left\lbrack {{Mathmatic}\mspace{14mu}{Formula}\mspace{14mu} 3} \right\rbrack\end{matrix}$

CPE values for evaluating cytotoxicity were calculated using thefollowing Mathematic Formula 4:

$\begin{matrix}{{\%\mspace{14mu}{CPE}} = {100 \times \frac{{OD}_{CC} - {OD}_{compound}}{{OD}_{CC} - {OD}_{Blank}}}} & \left\lbrack {{Mathmatic}\mspace{14mu}{Formula}\mspace{14mu} 4} \right\rbrack\end{matrix}$

In Formulas 3 and 4,

OD_(CC) corresponds to the OD of the uninfected and untreated,background cell cultures,

OD_(VC) represents the OD of the infected and untreated control cellcultures,

OD_(virus+Compound) represents the OD of the virus-infected cellcultures treated with a given concentration of compound, and

ODBlank represents the OD of the well added with the cell culture mediumalone.

The 50% effective concentration (EC₅₀) and the 50% cytotoxicconcentration (CC₅₀) were defined as the concentrations of compound thatoffered 50% protection against virus-induced CPE and that killed cellsby 50%, respectively, and were calculated using logarithmicinterpolation.

CC₅₀ and EC₅₀ against various viruses of some compounds are given inTable 3, below.

TABLE 5 Ex. 10 Ex. 46 Ex. 66 CC₅₀ [μM] >100  >100 >100 Coxsackie B3^(c)EC₅₀ [μM] 0.021 ± 0.0072 0.0026 ± 0.0012  0.0033 ± 0.0013  CoxsackieA16^(d) EC₅₀ [μM] 0.090 ± 0.035  — — Coxsackie A9^(f) EC₅₀ [μM] — 0.0017 ± 0.000037 0.0083 ± 0.00043 Coxsackie A21^(d) EC₅₀ [μM] 1.1 ±0.58 — — Entero 71^(e) EC₅₀ [μM] 0.012 ± 0.0020 0.0031 ± 0.00034  0.025± 0.00092 Echo 9^(d) EC₅₀ [μM] 0.025 ± 0.0057 0.0035 ± 0.00057 — Echo11^(f) EC₅₀ [μM] 0.021 ± 0.083  0.0023 ± 0.00088 0.0072 ± 0.00018 Polio1^(f) EC₅₀ [μM] 0.75 ± 0.37  0.068 ± 0.0072 0.69 ± 0.17  Polio 2^(f)EC₅₀ [μM] 0.36 ± 0.15  0.018 ± 0.0019 0.23 ± 0.020 Polio 3^(f) EC₅₀ [μM]1.0 ± 0.57 0.043 ± 0.017   0.58 ± 0.0069 Rhino 2^(g) EC₅₀ [μM] >50 >105.9 ± 0.25 Rhino 9^(g) EC₅₀ [μM] >50 3.5 ± 0.15 2.3 ± 0.70 Rhino 15^(g)EC₅₀ [μM] >50 2.8 ± 0.26 4.6 ± 1.3  Rhino 29^(g) EC₅₀ [μM] >50 4.6 ±0.72 6.4 ± 0.83 Rhino 39^(g) EC₅₀ [μM] >50 3.0 ± 0.17 1.8 ± 0.37 Rhino41^(g) EC₅₀ [μM] 8.8 ± 0.12 0.47 ± 0.036 0.60 ± 0.026 Rhino 45^(g) EC₅₀[μM] 3.4 ± 1.5  <0.078 1.7 ± 0.46 Rhino 59^(g) EC₅₀ [μM] — — >10 Rhino63^(g) EC₅₀ [μM] >50 8.5 ± 0.13 >10 Rhino 85^(g) EC₅₀ [μM] >50 6.2 ±0.70 >5.8 Rhino 89^(g) EC₅₀ [μM] >50 0.34 ± 0.86  0.63 ± 0.023 Rhino14^(g) EC₅₀ [μM] — <0.01 — Rhino 42^(g) EC₅₀ [μM] >50 — 0.15 ± 0.023Rhino 70^(g) EC₅₀ [μM] 2.4 ± 0.36 >0.078 0.057 ± 0.017  Rhino 72^(g)EC₅₀ [μM] 5.3 ± 1.2  — 0.13 ± 0.069 Rhino 86^(g) EC₅₀ [μM]  8 ± 2.9 —0.070 ± 0.0066

In Table 5, the superscript c represents incubation at 37° C. in Verocells, the superscript d represents incubation at 37° C. in MRC-5 cells,the superscript e represents incubation at 37° C. in RD cells, thesuperscript f represents incubation at 37° C. in BGM cells, thesuperscript g represents incubation at 37° C. in HeLa cells, and thesuperscript i represents 100% inhibition of viral replication withcompounds of 0.078 μM or higher.

As can be seen in Table 5, the indanone derivatives according to thepresent invention are low in cytotoxicity because their CC₅₀ wasmeasured at 100 μM or higher. In addition, the indanone derivatives wereobserved to have an EC₅₀ of 1.1 μM or less against coxsackieviruses B3,A16, A9, and A²¹. Particularly high antiviral activity was detected inthe compound of Example 46 with an EC₅₀ of as low as 0.0017 μM.

With regard to enterovirus 71, the indanone derivatives according to thepresent invention showed an EC₅₀ of 0.025 μM or less. Particularly highantiviral activity was detected in the compound of Example 46 with anEC₅₀ of as low as 0.0031 μM.

The indanone derivatives according to the invention showed an EC₅₀ of0.025 μM or less against echovirus 9 and echovirus 11, while the highestantiviral activity was detected in the compound of Example 46 asdemonstrated by the EC₅₀ of 0.0035 μM.

In the case of polioviruses 1, 2 and 3, EC₅₀ values of the indanonederivatives according to present invention were measured to be 1.0 μM orless. Particularly high antiviral activity was detected in the compoundof Example 46 with an EC₅₀ of as low as 0.068 μM.

Also, the indanone derivatives according to the invention were highlyinhibitory of rhinoviruses. For example, the compound of Example 46 hadan EC₅₀ of 0.078 μM or less against rhinoviruses 45 and 70.

Consequently, the indanone derivatives of the present invention are oflow cytotoxicity and exhibit excellent antiviral activity againstpicornaviruses including coxsackie-, entero-, echo-, polio- andrhinoviruses, so that they can be usefully applied to the prevention ortreatment of picornavirus-caused respiratory, cardiocirculatory, andnervous system diseases, including poliomyelitis, paralysis, acutehemorrhagic conjunctivitis, viral meningitis, hand-foot-and-mouthdisease, vesicular disease, hepatitis A, myositis, myocarditis,pancreatitis, diabetes, epidemic myalgia, encephalitis, cold,herpangina, foot-and-mouth disease, asthma, chronic obstructivepulmonary disease, pneumonia, sinusitis and otitis media.

<Formulation Example 1> Preparation of Pharmaceutical Formulations

<1-1> Preparation of Powder

Indanone derivative of Chemical Formula 1:2 g

Lactose: 1 g

The above ingredients were mixed and loaded into an airtight sac toproduce a powder agent.

<1-2> Preparation of Tablet

Indanone derivative of Chemical Formula 1:100 mg

Corn starch: 100 mg

Lactose: 100 mg

Mg stearate: 2 mg

These ingredients were mixed and prepared into tablets using a typicaltabletting method.

<1-3> Preparation of Capsule

Indanone derivative of Chemical Formula 1:100 mg

Corn starch: 100 mg

Lactose: 100 mg

Mg stearate: 2 mg

These ingredients were mixed and loaded into gelatin capsules accordingto a typical method to produce capsules.

<1-4> Preparation of Injection

Indanone derivative of Chemical Formula 1: 10 μg/ml

Diluted Hydrochloric acid BP: to be pH 3.5

Sodium chloride BP for injection: maximum 1 ml

The indanone derivative of the present invention was dissolved in aappropriate volume of sodium chloride BP for injection. The pH of theresultant solution was regulated to be pH 3.5 with dil.HCl BP, and thenits volume was regulated with sodium chloride BP for Injection and thesolution was mixed completely. The solution was then filled in 5-ml type1 ample that is made of transparent glass. The air was sealed in upperlattice by melting the glass. The solution contained in ample wasautoclaved at 120° C. for 15 min or more to be sterilized and thereby toobtain an injection.

INDUSTRIAL APPLICABILITY

Having excellent inhibitory activity against picornaviruses includingcoxsackie-, entero-, echo-, Polio-, and rhinoviruses, as well asexhibiting low cytotoxicity, as described hitherto, the indanonederivative of Chemical Formula 1 can be useful as an active ingredientof a pharmaceutical composition for the prevention or treatment of viraldiseases including poliomyelitis, paralysis, acute hemorrhagicconjunctivitis, viral meningitis, hand-foot-and-mouth disease, vesiculardisease, hepatitis A, myositis, myocarditis, pancreatitis, diabetes,epidemic myalgia, encephalitis, cold, herpangina, foot-and-mouthdisease, asthma, chronic obstructive pulmonary disease, pneumonia,sinusitis or otitis media.

The invention claimed is:
 1. A compound represented by the followingChemical Formula 1, a pharmaceutically acceptable salt thereof, or anenantiomer thereof:

wherein, A¹, A², and A³ are, independently or optionally, selected fromthe group consisting of —H, halogen, —OH, —CN, —N₃, C₁-C₁₀ alkoxy,linear or branched C₁-C₁₀ alkyl, 5-7-membered heterocycloalkylunsubstituted or substituted with —OH or methoxyphenylalkyl, C₆-C₁₂aryl, —O(C═O)R¹, —(C═O)R¹, —(C═O)OR¹, —O(C═O)OR¹, —O(C═O)NR¹R², —NO₂,—NR¹R², —NR¹(C═O)R², —NR¹(C═S)R², —NR¹(C═O)OR², —NR¹(C═O)—NR²R³,—NR¹(SO₂)R², and —NR¹(C═S)—NR²R³, with a proviso that at least two ofA¹, A², and A³ may form a ring together if they are adjacent to eachother; A⁴ is —NR¹R²; D is —OH, halogen, linear or branched C₁-C₁₀ alkyl,C₁-C₁₀ alkoxy unsubstituted or substituted with phenyl, —O(CH₂)_(n)OH,—O(C═O)R¹, —(C═O)R¹, —(C═O)OR¹, —O(C═O)OR¹, —O(C═O)NR¹R², —NO₂, —NR¹R²,—NR¹(O)R², —NR¹(C═O)R², —NR¹(C═S)R², —NR¹(C═O)OR², —NR¹(C═O)—NR¹R², or—NR¹(C═S)—NR¹R²; E is halogen, —OH, —CN, —N═C═O, —N₃, C₁-C₁₀ alkoxy,—O(C═O)R¹, —(C═O)R¹, —(C═O)OR¹, —O(C═O)OR¹, —O(C═O)NR¹R², —NO₂, —NR¹R²,—NR¹(C═O)R², —NR¹(C═S)R², —NR¹(C═O)OR², —NR¹(C═O)—NR¹R²,—NR¹(C═O)NR²OR³, —NR¹(SO₂)R², —NR¹(C═S)—NR¹R², —NR¹(P═O)(OR²)₂, or

G¹, G³, and G⁴ are independently or optionally selected from the groupconsisting of —H, halogen, —OH, CN, C₁-C₁₀ alkoxy, linear or branchedC₁-C₂₀ alkyl, C₆-C₁₂ aryl, —O(C═O)R¹, —(C═O)R¹, —(C═O)OR¹,—(CH₂)_(n)—(C═O)OR¹, —O(C═O)OR¹, —O(C═O)NR¹R², —NO₂, —NR¹R²,—NR¹(C═O)R², —NR¹(C═S)R², —NR¹(C═O)OR², —NR¹(C═O)—NR²R³, and—NR¹(C═S)—NR²R³; G² is selected from the group consisting of halogen,—OH, CN, C₁-C₁₀ alkoxy, branched C₃-C₂₀ alkyl, C₆-C₁₂ aryl, —O(C═O)R¹,—(C═O)R¹, —(C═O)OR¹, —(CH₂)_(n)—(C═O)OR¹, —O(C═O)OR¹, —O(C═O)NR¹R²,—NO₂, —NR¹R², —NR¹(C═O)R², —NR¹(C═S)R², —NR¹(C═O)OR², —NR¹(C═O)—NR²R³,and —NR¹(C═S)—NR²R³; X is hydrogen, oxygen, sulfur, hydroxy, linear orbranched C₁-C₁₀ alkyl, linear or branched C₁-C₁₀ alkylene, ═N—NR¹R²,—NR¹—OR², or ═N—OR¹; Y is —O—; R⁵ is —(C═O)H, —(C═O)OH, —(C═O)R¹,—(C═S)R¹, or —(C═O)OR¹; Z is C or N; R¹, R², R³, and R⁴ areindependently hydrogen, linear or branched C₁-C₁₀ alkyl, linear orbranched C₁-C₁₀ alkylene unsubstituted or substituted with phenyl, C₃-C₇cycloalkyl, C₃-C₇ heterocycloalkyl, C₆-C₁₂ aryl, or 5-14-memberedheteroaryl; wherein the heterocycloalkyl may be substituted with atleast one oxygen atom via a double bond, the aryl is mono- or bicyclicand may have at least one substituent selected from the group consistingof halogen, —CN, phenyl, linear or branched C₁-C₆ alkyl, R⁵, and C₁-C₆alkoxy, the heteroaryl is mono-, bi- or tricyclic, and may have at leastone substituent selected from the group consisting of halogen, —OH,—NO₂, —NH₂, —CN, ═O or —O⁻, linear or branched C₁-C₁₀ alkyl, linear orbranched C₁-C₁₀ alkoxy, and phenyl, the linear or branched alkyl may beunsubstituted or substituted with at least one substituent selected fromthe group consisting of phenyl, halogen, 5-7-membered heteroaryl, and—NHBoc, the phenyl may be substituted with at least one substituentselected from the group consisting of halogen, phenyl, orphenyl-substituted C₁-C₆ alkoxy, the heterocycloalkyl or heteroarylcontains at least one heteroatom selected from the group consisting ofN, O, and S, the halogen is F, Cl, Br, or I, n is an integer of 1-10,and ‘

’ represents a single or double bond; wherein when Z is N, A⁴ is notpresent.
 2. The compound, pharmaceutically acceptable salt, orenantiomer of claim 1, wherein A¹, A², and A³ are, independently oroptionally, selected from the group consisting of —H, C₁-C₅ alkoxy,linear or branched C₁-C₅ alkyl, 5-7-membered heterocycloalkylunsubstituted or substituted with —OH or methoxyphenylalkyl, C₆-C₁₂aryl, —NO₂, and —NR¹R²; D is —OH, halogen, linear or branched C₁-C₅alkyl, or C₁-C₅ alkoxy unsubstituted or substituted with phenyl; E ishalogen, —OH, C₁-C₅ alkoxy, —NR¹(C═O)R², —NR¹(C═O)OR², or—NR¹(C═O)—NR¹R²; G¹, G³, and G⁴ are, independently or optionally,selected from the group consisting of —H, C₁-C₅ alkoxy, and linear orbranched C₁-C₁₆ alkyl; G² is C₁-C₅ alkoxy or isopropyl; X is oxygen,hydroxyl, or linear or branched C₁-C₅ alkyl; Z is C or N; R¹, R², R³,and R⁴ are independently hydrogen, linear or branched C₁-C₇ alkyl, C₃-C₇heterocycloalkyl, C₆-C₁₂ aryl, or 5-14-membered heteroaryl; wherein theheterocycloalkyl may be substituted with at least one oxygen atom via adouble bond, the aryl is mono- or bicyclic and may have at least onesubstituent selected from the group consisting of halogen, phenyl,linear or branched C₁-C₃ alkyl, and C₁-C₃ alkoxy, the heteroaryl ismono-, bi- or tricyclic, and may have at least one substituent selectedfrom the group consisting of halogen, —OH, —NO₂, —NH₂, —CN, ═O or —O⁻,linear or branched C₁-C₁₀ alkyl, linear or branched C₁-C₁₀ alkoxy, andphenyl, the linear or branched alkyl may be unsubstituted or substitutedwith at least one substituent selected from the group consisting ofphenyl, halogen, and 5-7-membered heteroaryl, the phenyl may besubstituted with at least one substituent selected from the groupconsisting of halogen, and phenyl, the heterocycloalkyl or heteroarylcontains at least one heteroatom selected from the group consisting ofN, O, and S, the halogen is F, or Cl, and ‘

’ represents a single or double bond.
 3. The compound, pharmaceuticallyacceptable salt, or enantiomer of claim 1, wherein A¹, A², and A³ are,independently or optionally, selected from the group consisting of —Hand —NR¹R²; D is —OH; E is —OH or —NR¹(C═O)R²; G¹, G³, and G⁴ are,independently or optionally, linear or branched C₁-C₁₅ alkyl; G² isisopropyl; X is oxygen; Z is C; R¹, R², R³, and R⁴ are, independently,hydrogen or 5-14-membered heteroaryl; wherein, the 5-14-memberedheteroaryl is monocyclic, bicyclic, or tricyclic, and may be substitutedwith a substituent selected from the group consisting of halogen, —OH,—NO₂, —NH₂, —CN, ═O or —O⁻, linear or branched C₁-C₁₀ alkyl, linear orbranched C₁-C₁₀ alkoxy, and phenyl, the phenyl may be substituted withat least one substituent selected form the group consisting of halogenand phenyl, the heteroaryl contains a heteroatom selected from the groupconsisting of N, O, and S, and the halogen is F or Cl, and ‘

’ represents a single or double bond.
 4. The compound, pharmaceuticallyacceptable salt, or enantiomer of claim 1, wherein A¹, A², and A³ are—H, and A⁴ is —NH₂; D is —OH; E is —NR¹(C═O)R²; G¹, G³ and G⁴ are —H,and G² is isopropyl; X is oxygen; Z is C; R¹ is hydrogen and R² is5-14-membered heteroaryl; wherein the heteroaryl is furane, benzofurane,pyridine, pyrazolopyridine, pyrimidine, pyrazolopyrimidine, pyrazine,thiopene, quinoline, isoquinoline, triazole, thiazole, indole, pyrazole,indazole, tetrazole, benzotriazole, chromene, pyrane, pyrrole,benzopyrazole, isoxazole, xanthene, cinnoline, imidazole,benzoimidazole, acridine, imidazopyridine, imidazopyrimidine,quinoxaline, pyridazine, tetrazolopyridine, triazolopyridine,triazolopyrimidine or indolizine, and may be substituted with at leastone substituent selected from the group consisting of halogen, —OH,—NO₂, —NH₂, —CN, ═O or —O⁻, linear or branched C₃-C₁₀ alkyl, linear orbranched C₁-C₁₀ alkoxy, and phenyl, and the halogen is F or Cl, and ‘

’ represents a double bond.
 5. The compound, pharmaceutically acceptablesalt, or enantiomer of claim 1, wherein the compound is selected fromthe group consisting of:9b-hydroxy-7-isopropyl-4b-methoxy-1-nitro-4bH-benzo[d]indeno[1,2-b]furan-10(9bH)-one;1-amino-4b,9b-dihydroxy-7-isopropyl-4bH-benzo[d]indeno[1,2-b]furan-10(9bH)-one;1-amino-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furane-4b,9b-diyldiacetate;7-ethyl-4b,9b-dihydroxy-1-nitro-4b,9b-dihydro-5-oxa-indeno[2,1-a]inden-10-one;1-amino-4b,9b-dihydroxy-7-isopropyl-2-nitro-4bH-indeno[1,2-b]benzofuran-10(9bH)-one;1,4-diamino-4b,9b-dihydroxy-7-isopropyl-4bH-benzo[d]indeno[1,2-b]furan-10(9bH)-one;1,2-diamino-4b,9b-dihydroxy-7-isopropyl-4bH-indeno[1,2-b]benzofuran-10(9bH)-one;N-(1-amino-9b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-5-oxa-indeno[2,1-a]inden-4b-yl)-acetamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-4b,10-dihydro-5-oxa-indeno[2,1-a]inden-9b-yl)-isobutylamide;pentanoic acid(1-amino-4b-hydroxy-7-isopropyl-10-oxo-4b,10-dihydro-5-oxa-indeno[2,1-a]inden-9b-yl)-amide;1-amino-7-isopropyl-10-oxo-9b-pentanamido-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-4b-ylpentanoate;1-amino-9b-hexanamido-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-4b-ylhexanoate;1-amino-9b-heptanamido-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-4b-ylheptanoate;9b-acetamido-1-amino-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-4b-ylmethyl carbonate;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)pivalamide;9b-acetamido-1-amino-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-4b-ylbutyl carbonate;9b-acetamido-1-amino-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-4b-ylethyl carbonate;4b,9b-dihydroxy-7-isopropyl-4bH-benzofuro[2′,3′:3,4]cyclopenta[1,2-b]pyridin-10(9bH)-one;1-(ethylamino)-4b,9b-dihydroxy-7-isopropyl-4bH-indeno[1,2-b]benzofuran-10(9bH)-one;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)propionamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)butyramide;1-(dimethylamino)-4b,9b-dihydroxy-7-isopropyl-4bH-benzo[d]indeno[1,2-b]-furan-10(9bH)-one;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)benzamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-3-methoxybenzamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-4-chlorobenzamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)cyclopropanecarboxamide;1-(4b-hydroxy-6,8-diisopropyl-1-amino-10-oxo-9b,10-dihydro-4bH-benzo[d]-indeno[1,2-b]furan-9b-yl)-3-(4-methoxyphenyl)thiourea;1-(4b-hydroxy-6,8-diisopropyl-1-amino-10-oxo-9b,10-dihydro-4bH-benzo[d]-indeno[1,2-b]furan-9b-yl)-3-(phenyl)thiourea;1-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-3-(4-methoxyphenyl)urea;1-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-3-butylurea;1-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-3-(4-fluorophenyl)urea;1-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-3-(tert-butyl)urea;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)formamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)methanesulfonamide;diethyl(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)phosphoamidate;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-4-cyanobenzamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-2-naphthamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-[1,1′-biphenyl]-4-carboxamide;1-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)-3-ethylurea;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)tetrahydrofurane-2-carboxamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-2,2,2-trifluoroacetamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)-1,1,1-trifluoromethanesulfonamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-2-phenylacetamide;(E)-N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-3-(3,4-dichlorophenyl)acrylamide;2-([1,1′-biphenyl]-4-yl)-N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)acetamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-2-methoxybenzamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)-2-methylbenzamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)-3-methylbenzamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)-4-methylbenzamide;methyl-4-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-ylcarbamoyl)benzoate;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-3-chlorobenzamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-3,5-dimethylbenzamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-2,4,6-trichlorobenzamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)-2-fluoroacetamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)-2-chloroacetamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)picolinamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)nicotinamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)isonicotinamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)pirazine-2-carboxamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)furane-2-carboxamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)quinoline-8-carboxamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)quinoline-6-carboxamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)benzofurane-2-carboxamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)-3-methylbenzofurane-2-carboxamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-4-methylthiazole-5-carboxamide;(4R)—N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-2-oxothiazolidine-4-carboxamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)-1H-indazole-3-carboxamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)-2-(1H-tetrazol-1-yl)acetamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)quinoline-3-carboxamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)quinoline-4-carboxamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-5-methylthiophene-2-carboxamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-2-methoxythiophene-3-carboxamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-3-(2-chloro-6-fluorophenyl)-5-methylisooxazole-4-carboxamide;5-amino-N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)furane-2-carboxamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-1H-pyrrole-2-carboxamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-2-methoxyisonicotinamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)benzo[b]thiophene-2-carboxamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)-9H-xanthene-9-carboxamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)cinnoline-4-carboxamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)acridine-9-carboxamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)-4-nitro-1H-pyrazole-3-carboxamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)-4-methylpicolinamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)-4-(trifluoromethyl)picolinamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)-5-cyanopicolinamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)-3-chloropicolinamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)-4-methoxyquinoline-2-carboxamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)isoquinoline-3-carboxamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-2-methylisonicotinamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-3-fluoroisonicotinamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-3-chloroisonicotinamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-1-methyl-1H-imidazole-2-carboxamide;2-((1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)carbamoyl)pyridine1-oxide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-4-chloronicotinamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-5-fluoronicotinamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-5-hydroxynicotinamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-3-hydroxypicolinamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-4-methylnicotinamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-5-methylnicotinamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-5-methoxynicotinamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)quinoline-2-carboxamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)-3-bromobenzo[b]thiophene-2-carboxamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)-1H-indole-2-carboxamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)isoquinoline-1-carboxamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-6-fluoro-4-methoxyquinoline-3-carboxamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-1-methyl-1H-indole-2-carboxamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-3-chloro-6-fluorobenzo[b]thiophene-2-carboxamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-3-chloro-6-methylbenzo[b]thiophene-2-carboxamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-1,3-dimethyl-1H-pyrazolo[3,4-b]pyridine-5-carboxamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)imidazo[1,2-a]pyridine-6-carboxamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)pyrazolo[1,5-a]pyrimidine-2-carboxamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-3-methylbenzo[b]thiophene-2-carboxamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)quinoxaline-2-carboxamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)pyridazine-4-carboxamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)quinoxaline-6-carboxamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)tetrazolo[1,5-a]pyridine-6-carboxamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)tetrazolo[1,5-a]pyridine-8-carboxamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-7-methylimidazo[1,2-a]pyridine-2-carboxamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-7-methyl-[1,2,4]triazolo[1,5-a]pyrimidine-2-carboxamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-5,7-dimethylpyrazolo[1,5-a]pyrimidine-3-carboxamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)indolizine-2-carboxamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-1,6-diisopropyl-1H-pyrazolo[3,4-b]pyridine-4-carboxamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)imidazo[1,2-a]pyrimidine-2-carboxamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-1-oxo-1,2-dihydroisoquinoline-3-carboxamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)-3-methylimidazo[1,5-a]pyridine-1-carboxamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)-2H-indazole-3-carboxamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-7-methylpyrazolo[1,5-a]pyrimidine-6-carboxamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-1H-benzo[d]imidazole-2-carboxamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-5-fluoro-1H-benzo[d]imidazole-2-carboxamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)tetrazolo[1,5-a]pyridine-5-carboxamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-1-methyl-1H-indazole-3-carboxamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-1H-indole-5-carboxamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-1-methyl-3a,7a-dihydro-1H-indazole-3-carboxamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-1-methyl-1H-imidazole-4-carboxamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-1H-pyrrole-3-carboxamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-1H-indazole-5-caboxamide;andN-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-3-methyl-1H-pyrazole-5-carboxamide.6. The compound, pharmaceutically acceptable salt, or enantiomer ofclaim 1, wherein the compound is selected from the group consisting of:9b-hydroxy-7-isopropyl-4b-methoxy-1-nitro-4bH-benzo[d]indeno[1,2-b]furan-10(9bH)-one;1-amino-4b,9b-dihydroxy-7-isopropyl-4bH-benzo[d]indeno[1,2-b]furan-10(9bH)-one;1-amino-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furane-4b,9b-diyldiacetate;7-ethyl-4b,9b-dihydroxy-1-nitro-4b,9b-dihydro-5-oxa-indeno[2,1-a]inden-10-one;1-amino-4b,9b-dihydroxy-7-isopropyl-2-nitro-4bH-indeno[1,2-b]benzofuran-10(9bH)-one;1,4-diamino-4b,9b-dihydroxy-7-isopropyl-4bH-benzo[d]indeno[1,2-b]furan-10(9bH)-one;1,2-diamino-4b,9b-dihydroxy-7-isopropyl-4bH-indeno[1,2-b]benzofuran-10(9bH)-one;N-(1-amino-9b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-5-oxa-indeno[2,1-a]inden-4b-yl)-acetamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-4b,10-dihydro-5-oxa-indeno[2,1-a]inden-9b-yl)-isobutylamide;pentanoic acid(1-amino-4b-hydroxy-7-isopropyl-10-oxo-4b,10-dihydro-5-oxa-indeno[2,1-a]inden-9b-yl)-amide;1-amino-7-isopropyl-10-oxo-9b-pentanamido-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-4b-ylpentanoate;1-amino-9b-hexanamido-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-4b-ylhexanoate;1-amino-9b-heptanamido-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-4b-ylheptanoate;9b-acetamido-1-amino-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-4b-ylmethyl carbonate;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)pivalamide;9b-acetamido-1-amino-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-4b-ylbutyl carbonate;9b-acetamido-1-amino-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-4b-ylethyl carbonate;4b,9b-dihydroxy-7-isopropyl-4bH-benzofuro[2′,3′:3,4]cyclopenta[1,2-b]pyridin-10(9bH)-one;1-(ethylamino)-4b,9b-dihydroxy-7-isopropyl-4bH-indeno[1,2-b]benzofuran-10(9bH)-one;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)propionamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)butyramide;1-(dimethylamino)-4b,9b-dihydroxy-7-isopropyl-4bH-benzo[d]indeno[1,2-b]-furan-10(9bH)-one;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)benzamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-3-methoxybenzamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-4-chlorobenzamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)cyclopropanecarboxamide;1-(4b-hydroxy-6,8-diisopropyl-1-amino-10-oxo-9b,10-dihydro-4bH-benzo[d]-indeno[1,2-b]furan-9b-yl)-3-(4-methoxyphenyl)thiourea;1-(4b-hydroxy-6,8-diisopropyl-1-amino-10-oxo-9b,10-dihydro-4bH-benzo[d]-indeno[1,2-b]furan-9b-yl)-3-(phenyl)thiourea;1-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-3-(4-methoxyphenyl)urea;1-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-3-butylurea;1-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-3-(4-fluorophenyl)urea;1-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-3-(tert-butyl)urea;1-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)formamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)formamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)methanesulfonamide;diethyl(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)phosphoamidate;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-4-cyanobenzamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-2-naphthamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-[1,1′-biphenyl]-4-carboxamide;1-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)-3-ethylurea;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)tetrahydrofurane-2-carboxamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-2,2,2-trifluoroacetamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)-1,1,1-trifluoromethanesulfonamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-2-phenylacetamide;(E)-N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-3-(3,4-dichlorophenyl)acrylamide;2-([1,1′-biphenyl]-4-yl)-N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)acetamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-2-methoxybenzamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)-2-methylbenzamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)-3-methylbenzamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)-4-methylbenzamide;methyl-4-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-ylcarbamoyl)benzoate;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-3-chlorobenzamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-3,5-dimethylbenzamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-2,4,6-trichlorobenzamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)-2-fluoroacetamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)-2-chloroacetamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)picolinamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)nicotinamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)isonicotinamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)pirazine-2-carboxamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)furane-2-carboxamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)quinoline-8-carboxamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)quinoline-6-carboxamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)benzofurane-2-carboxamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)-3-methylbenzofurane-2-carboxamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-4-methylthiazole-5-carboxamide;(4R)—N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-2-oxothiazolidine-4-carboxamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)-1H-indazole-3-carboxamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)-2-(1H-tetrazol-1-yl)acetamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)quinoline-3-carboxamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)quinoline-4-carboxamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-5-methylthiophene-2-carboxamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-2-methoxythiophene-3-carboxamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-3-(2-chloro-6-fluorophenyl)-5-methylisooxazole-4-carboxamide;5-amino-N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)furane-2-carboxamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-1H-pyrrole-2-carboxamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-2-methoxyisonicotinamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)benzo[b]thiophene-2-carboxamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)-9H-xanthene-9-carboxamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)cinnoline-4-carboxamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)acridine-9-carboxamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)-4-nitro-1H-pyrazole-3-carboxamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)-4-methylpicolinamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)-4-(trifluoromethyl)picolinamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)-5-cyanopicolinamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)-3-chloropicolinamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)-4-methoxyquinoline-2-carboxamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)isoquinoline-3-carboxamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-2-methylisonicotinamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-3-fluoroisonicotinamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-3-chloroisonicotinamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-1-methyl-1H-imidazole-2-carboxamide;2-((1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)carbamoyl)pyridine1-oxide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-4-chloronicotinamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-5-fluoronicotinamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-5-hydroxynicotinamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-3-hydroxypicolinamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-4-methylnicotinamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-5-methylnicotinamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-5-methoxynicotinamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)quinoline-2-carboxamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)-3-bromobenzo[b]thiophene-2-carboxamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)-1H-indole-2-carboxamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)isoquinoline-1-carboxamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-6-fluoro-4-methoxyquinoline-3-carboxamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-1-methyl-1H-indole-2-carboxamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-3-chloro-6-fluorobenzo[b]thiophene-2-carboxamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-3-chloro-6-methylbenzo[b]thiophene-2-carboxamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-1,3-dimethyl-1H-pyrazolo[3,4-b]pyridine-5-carboxamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)imidazo[1,2-a]pyridine-6-carboxamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)pyrazolo[1,5-a]pyrimidine-2-carboxamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-3-methylbenzo[b]thiophene-2-carboxamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)quinoxaline-2-carboxamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)pyridazine-4-carboxamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)quinoxaline-6-carboxamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)tetrazolo[1,5-a]pyridine-6-carboxamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)tetrazolo[1,5-a]pyridine-8-carboxamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-7-methylimidazo[1,2-a]pyridine-2-carboxamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-7-methyl-[1,2,4]triazolo[1,5-a]pyrimidine-2-carboxamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-5,7-dimethylpyrazolo[1,5-a]pyrimidine-3-carboxamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)indolizine-2-carboxamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-1,6-diisopropyl-1H-pyrazolo[3,4-b]pyridine-4-carboxamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)imidazo[1,2-a]pyrimidine-2-carboxamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-1-oxo-1,2-dihydroisoquinoline-3-carboxamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)-3-methylimidazo[1,5-a]pyridine-1-carboxamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)-2H-indazole-3-carboxamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-7-methylpyrazolo[1,5-a]pyrimidine-6-carboxamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-1H-benzo[d]imidazole-2-carboxamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-5-fluoro-1H-benzo[d]imidazole-2-carboxamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)tetrazolo[1,5-a]pyridine-5-carboxamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-1-methyl-1H-indazole-3-carboxamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-1H-indole-5-carboxamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-1-methyl-3a,7a-dihydro-1H-indazole-3-carboxamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-1-methyl-1H-imidazole-4-carboxamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-1H-pyrrole-3-carboxamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-1H-indazole-5-caboxamide;andN-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-3-methyl-1H-pyrazole-5-carboxamide.7. The compound, pharmaceutically acceptable salt, or enantiomer ofclaim 1, wherein the compound is selected from the group consisting of:N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)picolinamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)nicotinamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)isonicotinamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)pirazine-2-carboxamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)furane-2-carboxamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)quinoline-8-carboxamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)quinoline-6-carboxamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)benzofurane-2-carboxamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)-3-methylbenzofurane-2-carboxamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-4-methylthiazole-5-carboxamide;(4R)—N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-2-oxothiazolidine-4-carboxamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)-1H-indazole-3-carboxamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)-2-(1H-tetrazol-1-yl)acetamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)quinoline-3-carboxamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)quinoline-4-carboxamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-5-methylthiophene-2-carboxamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-2-methoxythiophene-3-carboxamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-3-(2-chloro-6-fluorophenyl)-5-methylisooxazole-4-carboxamide;5-amino-N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)furane-2-carboxamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-1H-pyrrole-2-carboxamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-2-methoxyisonicotinamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)benzo[b]thiophene-2-carboxamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)-9H-xanthene-9-carboxamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)cinnoline-4-carboxamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)acridine-9-carboxamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)-4-nitro-1H-pyrazole-3-carboxamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)-4-methylpicolinamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)-4-(trifluoromethyl)picolinamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)-5-cyanopicolinamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)-3-chloropicolinamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)-4-methoxyquinoline-2-carboxamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)isoquinoline-3-carboxamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-2-methylisonicotinamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-3-fluoroisonicotinamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-3-chloroisonicotinamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-1-methyl-1H-imidazole-2-carboxamide;2-((1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)carbamoyl)pyridine1-oxide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-4-chloronicotinamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-5-fluoronicotinamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-5-hydroxynicotinamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-3-hydroxypicolinamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-4-methylnicotinamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-5-methylnicotinamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-5-methoxynicotinamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)quinoline-2-carboxamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)-3-bromobenzo[b]thiophene-2-carboxamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)-1H-indole-2-carboxamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)isoquinoline-1-carboxamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-6-fluoro-4-methoxyquinoline-3-carboxamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-1-methyl-1H-indole-2-carboxamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-3-chloro-6-fluorobenzo[b]thiophene-2-carboxamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-3-chloro-6-methylbenzo[b]thiophene-2-carboxamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-1,3-dimethyl-1H-pyrazolo[3,4-b]pyridine-5-carboxamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)imidazo[1,2-a]pyridine-6-carboxamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)pyrazolo[1,5-a]pyrimidine-2-carboxamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-3-methylbenzo[b]thiophene-2-carboxamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)quinoxaline-2-carboxamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)pyridazine-4-carboxamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)quinoxaline-6-carboxamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)tetrazolo[1,5-a]pyridine-6-carboxamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)tetrazolo[1,5-a]pyridine-8-carboxamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-7-methylimidazo[1,2-a]pyridine-2-carboxamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-7-methyl-[1,2,4]triazolo[1,5-a]pyrimidine-2-carboxamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-5,7-dimethylpyrazolo[1,5-a]pyrimidine-3-carboxamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)indolizine-2-carboxamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-1,6-diisopropyl-1H-pyrazolo[3,4-b]pyridine-4-carboxamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)imidazo[1,2-a]pyrimidine-2-carboxamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-1-oxo-1,2-dihydroisoquinoline-3-carboxamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)-3-methylimidazo[1,5-a]pyridine-1-carboxamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-benzo[d]indeno[1,2-b]furan-9b-yl)-2H-indazole-3-carboxamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-7-methylpyrazolo[1,5-a]pyrimidine-6-carboxamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-1H-benzo[d]imidazole-2-carboxamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-5-fluoro-1H-benzo[d]imidazole-2-carboxamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)tetrazolo[1,5-a]pyridine-5-carboxamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-1-methyl-1H-indazole-3-carboxamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-1H-indole-5-carboxamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-1-methyl-3a,7a-dihydro-1H-indazole-3-carboxamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-1-methyl-1H-imidazole-4-carboxamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-1H-pyrrole-3-carboxamide;N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-1H-indazole-5-caboxamide;andN-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-3-methyl-1H-pyrazole-5-carboxamide.8. A method of treating a viral disease in a patient, comprisingadministering a therapeutically effective amount of the compound,pharmaceutically acceptable salt, or enantiomer of claim 1 to thepatient.
 9. The method of claim 8, wherein the viral disease is causedby coxsackieviruses.
 10. The method of claim 8, wherein the viraldisease is caused by polioviruses.
 11. The method of claim 8, whereinthe viral disease is caused by echoroviruses.
 12. The method of claim 8,wherein the viral disease is caused by enteroviruses.
 13. The method ofclaim 8, wherein the viral disease is caused by rhinoviruses.
 14. Themethod of claim 8, wherein the viral disease is caused bypicornaviruses.
 15. The method of claim 8, wherein the viral disease ispoliomyelitis, paralysis, acute hemorrhagic conjunctivitis, viralmeningitis, hand-foot-and-mouth disease, vesicular disease, hepatitis A,myositis, myocarditis, pancreatitis, epidemic myalgia, encephalitis,cold, herpangina, foot-and-mouth disease, asthma, chronic obstructivepulmonary disease, pneumonia, sinusitis or otitis media.
 16. Thecompound, pharmaceutically acceptable salt, or enantiomer of claim 1,wherein D is —OH; E is —OH or —NR¹(C═O)R²; G² is isopropyl; and Z is C.17. The compound, pharmaceutically acceptable salt, or enantiomer ofclaim 1, wherein E is —OH; and G² is isopropyl.
 18. A pharmaceuticalcomposition comprising a therapeutically effective amount of thecompound of claim 1, a pharmaceutically acceptable salt thereof, or anenantiomer thereof, and a diluent or excipient.